DOI: 10.1084/jem.191.6.927. The Formation of Immunogenic Major Histocompatibility Complex Class II–Peptide Ligands in Lysosomal Compartments of Dendritic Cells Is Regulated by Inflammatory Stimuli

The Formation of Immunogenic Major Histocompatibility Complex Class II–Peptide Ligands in Lysosomal Compartments of Dendritic Cells Is Regulated by Inflammatory Stimuli

10.1084/jem.191.6.927

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

During their final differentiation or maturation, dendritic cells (DCs) redistribute their major histocompatibility complex (MHC) class II products from intracellular compartments to the plasma membrane. Using cells arrested in the immature state, we now find that DCs also regulate the initial intracellular formation of immunogenic MHC class II–peptide complexes. Immature DCs internalize the protein antigen, hen egg lysozyme (HEL), into late endosomes and lysosomes rich in MHC class II molecules. There, despite extensive colocalization of HEL protein and MHC class II products, MHC class II–peptide complexes do not form unless the DCs are exposed to inflammatory mediators such as tumor necrosis factor α, CD40 ligand, or lipoplolysaccharide. The control of T cell receptor (TCR) ligand formation was observed using the C4H3 monoclonal antibody to detect MHC class II–HEL peptide complexes by flow cytometry and confocal microscopy, and with HEL-specific 3A9 transgenic T cells to detect downregulation of the TCR upon MHC–peptide encounter. Even the binding of preprocessed HEL peptide to MHC class II is blocked in immature DCs, including the formation of C4H3 epitope in MHC class II compartments, suggesting an arrest to antigen presentation at the peptide-loading step, rather than an enhanced degradation of MHC class II–peptide complexes at the cell surface, as described in previous work. Therefore, the capacity of late endosomes and lysosomes to produce MHC class II–peptide complexes can be strictly controlled during DC differentiation, helping to coordinate antigen acquisition and inflammatory stimuli with formation of TCR ligands. The increased ability of maturing DCs to load MHC class II molecules with antigenic cargo contributes to the &gt;100-fold enhancement of the subsequent primary immune response observed when immature and mature DCs are compared as immune adjuvants in culture and in mice.

Bibliography

Inaba, K., Turley, S., Iyoda, T., Yamaide, F., Shimoyama, S., e Sousa, C. R., Germain, R. N., Mellman, I., & Steinman, R. M. (2000). The Formation of Immunogenic Major Histocompatibility Complex Class IIâPeptide Ligands in Lysosomal Compartments of Dendritic Cells Is Regulated by Inflammatory Stimuli. The Journal of Experimental Medicine, 191(6), 927â936.

Authors 9

Kayo Inaba (first)
Shannon Turley (additional)
Tomonori Iyoda (additional)
Fumiya Yamaide (additional)
Susumu Shimoyama (additional)
Caetano Reis e Sousa (additional)
Ronald N. Germain (additional)
Ira Mellman (additional)
Ralph M. Steinman (additional)

References 61 Referenced 324

10.1182/blood.V90.9.3245 / Blood. / Dendritic cellsunique leukocyte populations which control the primary immune response by Hart (1997)
10.1038/32588 / Nature. / Dendritic cells and the control of immunity by Banchereau (1998)
10.1084/jem.178.2.479 / J. Exp. Med. / Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo by Inaba (1993)
10.1084/jem.178.2.509 / J. Exp. Med. / Phagocytosis of antigens by Langerhans cells in vitro by Reis e Sousa (1993)
10.1084/jem.169.3.1169 / J. Exp. Med. / Presentation of exogenous protein antigens by dendritic cells to T cell clonesintact protein is presented best by immature, epidermal Langerhans cells by Romani (1989)
10.1084/jem.172.5.1459 / J. Exp. Med. / Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of major histocompatibility complex class II molecules and expression of invariant chain by Pure (1990)
10.1084/jem.184.4.1413 / J. Exp. Med. / Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo by De Smedt (1996)
10.1016/S0952-7915(97)80153-7 / Curr. Opin. Immunol. / Origin, maturation and antigen presenting function of dendritic cells by Cella (1997)
10.1084/jem.180.4.1263 / J. Exp. Med. / Activation of human dendritic cells through CD40 cross-linking by Caux (1994)
10.1084/jem.185.2.317 / J. Exp. Med. / Maturation stages of mouse dendritic cells in growth factor–dependent long-term cultures by Winzler (1997)
10.1084/jem.180.5.1849 / J. Exp. Med. / The tissue distribution of the B7-2 costimulator in miceabundant expression on dendritic cells in situ and during maturation in vitro by Inaba (1994)
10.1084/jem.180.5.1841 / J. Exp. Med. / B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells by Caux (1994)
10.1084/jem.184.2.747 / J. Exp. Med. / Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacityT-T help via APC activation by Cella (1996)
10.1084/jem.184.2.741 / J. Exp. Med. / High level IL-12 production by murine dendritic cellsupregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10 by Koch (1996)
10.1016/S0022-1759(98)00208-7 / J. Immunol. Methods. / Generation of large numbers of fully mature and stable dendritic cells from leukapheresis products for clinical application by Thurner (1999)
10.1084/jem.188.2.373 / J. Exp. Med. / Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites by Dieu (1998)
10.4049/jimmunol.161.6.3096 / J. Immunol. / EB11/CCR7 is a new member of dendritic cell chemokine receptor that is upregulated upon maturation by Yanagihara (1998)
10.1002/(SICI)1521-4141(199809)28:09<2760::AID-IMMU2760>3.0.CO;2-N / Eur. J. Immunol. / Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation by Sallusto (1998)
10.1126/science.284.5415.819 / Science. / Chemokine up-regulation and activated T cell attraction by maturing dendritic cells by Tang (1999)
10.1038/42030 / Nature. / Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells by Cella (1997)
10.1038/42039 / Nature. / Developmental regulation of MHC class II transport in mouse dendritic cells by Pierre (1997)
10.1016/S0092-8674(00)81458-0 / Cell. / Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells by Pierre (1998)
10.1038/345615a0 / Nature. / Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding by Roche (1990)
10.1084/jem.180.3.1107 / J. Exp. Med. / The CLIP region of invariant chain plays a critical role in regulating major histocompatibility complex class II folding, transport, and peptide occupancy by Romagnoli (1994)
10.1073/pnas.94.25.13856 / Proc. Natl. Acad. Sci. USA / Production, specificity, and functionality of monoclonal antibodies to specific peptide-major histocompatibility complex class II complexes formed by processing of exogenous protein by Zhong (1997)
10.1084/jem.186.5.673 / J. Exp. Med. / Antigen-unspecific B cells and lymphoid dendritic cells both show extensive surface expression of processed antigen–major histocompatibility class II complexes after soluble protein exposure in vivo or in vitro by Zhong (1997)
10.1084/jem.186.8.1183 / J. Exp. Med. / Dendritic cells as adjuvants for immune-mediated resistance to tumors by Schuler (1997)
10.1038/nm0398-328 / Nat. Med. / Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells by Nestle (1998)
10.1172/JCI6909 / J. Clin. Invest. / Rapid generation of broad T-cell immunity in humans after single injection of mature dendritic cells by Dhodopkar (1999)
10.1084/jem.190.11.1669 / J. Exp. Med. / Vaccination with Mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma by Thurner (1999)
10.1084/jem.176.6.1693 / J. Exp. Med. / Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor by Inaba (1992)
10.1084/jem.172.5.1483 / J. Exp. Med. / Migration and maturation of Langerhans cells in skin transplants and explants by Larsen (1990)
10.1111/1523-1747.ep12613452 / J. Invest. Dermatol. / Both dendritic cells and memory T lymphocytes emigrate from organ cultures of human skin and form distinctive dendritic-T-cell conjugates by Pope (1995)
10.1093/oxfordjournals.jbchem.a123191 / J. Biochem. / Tachyplesins isolated from hemocytes of Southeast Asian horseshoe crabs (Carcinoscorpius rotundicauda and Tachypleus gigas)identification of a new tachyplesin, tachyplesin III, and a processing intermediate of its precursor by Muta (1990)
10.1084/jem.179.5.1539 / J. Exp. Med. / Resting and anergic B cells are defective in CD28-dependent costimulation of naive CD4+ T cells by Ho (1994)
10.4049/jimmunol.162.11.6552 / J. Immunol. / Analysis of adjuvant function by direct visualization of antigen presentation in vivoendotoxin promotes accumulation of antigen-bearing dendritic cells in the T cell areas of lymphoid tissue by Reis e Sousa (1999)
{'key': '2023072509161712000_R37', 'article-title': 'Transport of peptide-MHC class II complexes in developing dendritic cells', 'volume': 'In press', 'author': 'Turley', 'year': '2000', 'journal-title': 'Science'} / Science / Transport of peptide-MHC class II complexes in developing dendritic cells by Turley (2000)
10.1016/0022-1759(96)00058-0 / J. Immunol. Methods. / An improved isolation method for murine migratory cutaneous dendritic cells by Ortner (1996)
10.1046/j.1523-1747.1998.00161.x / J. Invest. Dermatol. / Entry into afferent lymphatics and maturation in situ of migrating murine cutaneous dendritic cells by Weinlich (1998)
10.1084/jem.185.4.641 / J. Exp. Med. / Requirements for peptide-induced T cell receptor downregulation on naive CD8+ T cells by Cai (1997)
10.1016/S1074-7613(00)80461-6 / Immunity. / The duration of antigenic stimulation determines the fate of naive and effector T cells by Iezzi (1998)
10.1002/(SICI)1521-4141(199806)28:06<2025::AID-IMMU2025>3.0.CO;2-C / Eur. J. Immunol. / The chemokine SLC is expressed in T cell areas of lymph nodes amd mucosal lymphoid tissues and attracts activated T cells via CCR7 by Willimann (1998)
10.1084/jem.189.3.451 / J. Exp. Med. / Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization by Gunn (1999)
10.1146/annurev.cb.11.110195.001411 / Annu. Rev. Cell Dev. Biol. / How MHC class II molecules acquire peptide cargobiosynthesis and trafficking through the endocytic pathway by Wolf (1995)
10.1146/annurev.immunol.15.1.821 / Annu. Rev. Immunol. / Capture and processing of exogenous antigens for presentation on MHC molecules by Watts (1997)
10.1016/0092-8674(90)90137-4 / Cell. / MHC class II-associated invariant chain contains a sorting signal for endosomal compartments by Bakke (1990)
10.1084/jem.179.2.681 / J. Exp. Med. / The invariant chain is required for intracellular transport and function of major histocompatibility complex class II molecules by Elliot (1994)
10.1084/jem.185.3.429 / J. Exp. Med. / Related leucine-based cytoplasmic targeting signals in invariant chain and major histocompatibility complex class II molecules control endocytic presentation of distinct determinants in a single protein by Zhong (1997)
10.1038/343133a0 / Nature. / Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment by Guagliardi (1990)
10.1038/369120a0 / Nature. / Isolation and characterization of the intracellular MHC class II compartment by Tulp (1994)
10.1038/369113a0 / Nature / Transient accumulation of new class II MHC molecules in a novel endocytic compartment in B lymphocytes by Amigorena (1994)
10.1126/science.7985027 / Science. / Accumulation of HLA-DM, a regulator of antigen presentation, in MHC class II compartments by Sanderson (1994)
10.1016/S1074-7613(00)80431-8 / Immunity. / HLA-DM is localized to conventional and unconventional MHC class II-containing endocytic compartments by Pierre (1996)
10.1084/jem.182.2.389 / J. Exp. Med. / Dendritic cells use macropinocytosis and the mannose receptor to concentrate antigen in the major histocompatibility class II compartment. Downregulation by cytokines and bacterial products by Sallusto (1995)
10.1084/jem.182.1.163 / J. Exp. Med. / Antigen capture and MHC class II compartments of freshly isolated and cultured human blood dendritic cells by Nijman (1995)
10.1016/S1074-7613(00)80249-6 / Immunity. / Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading by Riese (1996)
10.1126/science.2113314 / Science / A cell culture model for T lymphocyte clonal anergy by Schwartz (1990)
10.1084/jem.178.5.1753 / J. Exp. Med. / B7 but not intercellular adhesion molecule-1 costimulation prevents the induction of human alloantigen–specific tolerance by Boussiotis (1993)
10.1084/jem.188.11.2163 / J. Exp. Med. / Efficient presentation of phagocytosed cellular fragments on the MHC class II products of dendritic cells by Inaba (1998)
10.1084/jem.186.2.239 / J. Exp. Med. / Class I–restricted cross-presentation of exogenous self-antigens leads to deletion of autoreactive CD8+ T cells by Kurts (1997)
10.1084/jem.186.5.665 / J. Exp. Med. / High levels of a major histocompatibility complex II–self-peptide complex on dendritic cells from the T cell areas of lymph nodes by Inaba (1997)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:48 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 6:31 a.m.)
Indexed	3 days, 21 hours ago (Aug. 28, 2025, 8:48 a.m.)
Issued	25 years, 5 months ago (March 13, 2000)
Published	25 years, 5 months ago (March 13, 2000)
Published Online	25 years, 5 months ago (March 13, 2000)
Published Print	25 years, 5 months ago (March 20, 2000)

Funders 0

None

BibTeX

@article{Inaba_2000, title={The Formation of Immunogenic Major Histocompatibility Complex Class II–Peptide Ligands in Lysosomal Compartments of Dendritic Cells Is Regulated by Inflammatory Stimuli}, volume={191}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.191.6.927}, DOI={10.1084/jem.191.6.927}, number={6}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Inaba, Kayo and Turley, Shannon and Iyoda, Tomonori and Yamaide, Fumiya and Shimoyama, Susumu and e Sousa, Caetano Reis and Germain, Ronald N. and Mellman, Ira and Steinman, Ralph M.}, year={2000}, month=mar, pages={927–936} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        28
      ]
    ],
    "date-time": "2025-08-28T12:48:49Z",
    "timestamp": 1756385329726
  },
  "reference-count": 61,
  "publisher": "Rockefeller University Press",
  "issue": "6",
  "content-domain": {
    "domain": [
      "rupress.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2000,
        3,
        20
      ]
    ]
  },
  "abstract": "<jats:p>During their final differentiation or maturation, dendritic cells (DCs) redistribute their major histocompatibility complex (MHC) class II products from intracellular compartments to the plasma membrane. Using cells arrested in the immature state, we now find that DCs also regulate the initial intracellular formation of immunogenic MHC class II\u2013peptide complexes. Immature DCs internalize the protein antigen, hen egg lysozyme (HEL), into late endosomes and lysosomes rich in MHC class II molecules. There, despite extensive colocalization of HEL protein and MHC class II products, MHC class II\u2013peptide complexes do not form unless the DCs are exposed to inflammatory mediators such as tumor necrosis factor \u03b1, CD40 ligand, or lipoplolysaccharide. The control of T cell receptor (TCR) ligand formation was observed using the C4H3 monoclonal antibody to detect MHC class II\u2013HEL peptide complexes by flow cytometry and confocal microscopy, and with HEL-specific 3A9 transgenic T cells to detect downregulation of the TCR upon MHC\u2013peptide encounter. Even the binding of preprocessed HEL peptide to MHC class II is blocked in immature DCs, including the formation of C4H3 epitope in MHC class II compartments, suggesting an arrest to antigen presentation at the peptide-loading step, rather than an enhanced degradation of MHC class II\u2013peptide complexes at the cell surface, as described in previous work. Therefore, the capacity of late endosomes and lysosomes to produce MHC class II\u2013peptide complexes can be strictly controlled during DC differentiation, helping to coordinate antigen acquisition and inflammatory stimuli with formation of TCR ligands. The increased ability of maturing DCs to load MHC class II molecules with antigenic cargo contributes to the &amp;gt;100-fold enhancement of the subsequent primary immune response observed when immature and mature DCs are compared as immune adjuvants in culture and in mice.</jats:p>",
  "DOI": "10.1084/jem.191.6.927",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T16:48:33Z",
    "timestamp": 1027702113000
  },
  "page": "927-936",
  "update-policy": "http://dx.doi.org/10.1084/jem.crossmarkpolicy",
  "source": "Crossref",
  "is-referenced-by-count": 324,
  "title": "The Formation of Immunogenic Major Histocompatibility Complex Class II\u2013Peptide Ligands in Lysosomal Compartments of Dendritic Cells Is Regulated by Inflammatory Stimuli",
  "prefix": "10.1084",
  "volume": "191",
  "author": [
    {
      "given": "Kayo",
      "family": "Inaba",
      "sequence": "first",
      "affiliation": [
        {
          "name": "aLaboratory of Immunobiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan"
        }
      ]
    },
    {
      "given": "Shannon",
      "family": "Turley",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "bDepartment of Cell Biology, Yale University Medical School, New Haven, Connecticut 06520-8002"
        }
      ]
    },
    {
      "given": "Tomonori",
      "family": "Iyoda",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "aLaboratory of Immunobiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan"
        }
      ]
    },
    {
      "given": "Fumiya",
      "family": "Yamaide",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "aLaboratory of Immunobiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan"
        }
      ]
    },
    {
      "given": "Susumu",
      "family": "Shimoyama",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "aLaboratory of Immunobiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan"
        }
      ]
    },
    {
      "given": "Caetano Reis",
      "family": "e Sousa",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "cLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892"
        }
      ]
    },
    {
      "given": "Ronald N.",
      "family": "Germain",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "cLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892"
        }
      ]
    },
    {
      "given": "Ira",
      "family": "Mellman",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "bDepartment of Cell Biology, Yale University Medical School, New Haven, Connecticut 06520-8002"
        }
      ]
    },
    {
      "given": "Ralph M.",
      "family": "Steinman",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "dLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399"
        }
      ]
    }
  ],
  "member": "291",
  "published-online": {
    "date-parts": [
      [
        2000,
        3,
        13
      ]
    ]
  },
  "reference": [
    {
      "key": "2023072509161712000_R1",
      "doi-asserted-by": "crossref",
      "first-page": "3245",
      "DOI": "10.1182/blood.V90.9.3245",
      "article-title": "Dendritic cellsunique leukocyte populations which control the primary immune response",
      "volume": "90",
      "author": "Hart",
      "year": "1997",
      "journal-title": "Blood."
    },
    {
      "key": "2023072509161712000_R2",
      "doi-asserted-by": "crossref",
      "first-page": "245",
      "DOI": "10.1038/32588",
      "article-title": "Dendritic cells and the control of immunity",
      "volume": "392",
      "author": "Banchereau",
      "year": "1998",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509161712000_R3",
      "doi-asserted-by": "crossref",
      "first-page": "479",
      "DOI": "10.1084/jem.178.2.479",
      "article-title": "Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo",
      "volume": "178",
      "author": "Inaba",
      "year": "1993",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R4",
      "doi-asserted-by": "crossref",
      "first-page": "509",
      "DOI": "10.1084/jem.178.2.509",
      "article-title": "Phagocytosis of antigens by Langerhans cells in vitro",
      "volume": "178",
      "author": "Reis e Sousa",
      "year": "1993",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R5",
      "doi-asserted-by": "crossref",
      "first-page": "1169",
      "DOI": "10.1084/jem.169.3.1169",
      "article-title": "Presentation of exogenous protein antigens by dendritic cells to T cell clonesintact protein is presented best by immature, epidermal Langerhans cells",
      "volume": "169",
      "author": "Romani",
      "year": "1989",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R6",
      "doi-asserted-by": "crossref",
      "first-page": "1459",
      "DOI": "10.1084/jem.172.5.1459",
      "article-title": "Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of major histocompatibility complex class II molecules and expression of invariant chain",
      "volume": "172",
      "author": "Pure",
      "year": "1990",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R7",
      "doi-asserted-by": "crossref",
      "first-page": "1413",
      "DOI": "10.1084/jem.184.4.1413",
      "article-title": "Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo",
      "volume": "184",
      "author": "De Smedt",
      "year": "1996",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R8",
      "doi-asserted-by": "crossref",
      "first-page": "10",
      "DOI": "10.1016/S0952-7915(97)80153-7",
      "article-title": "Origin, maturation and antigen presenting function of dendritic cells",
      "volume": "9",
      "author": "Cella",
      "year": "1997",
      "journal-title": "Curr. Opin. Immunol."
    },
    {
      "key": "2023072509161712000_R9",
      "doi-asserted-by": "crossref",
      "first-page": "1263",
      "DOI": "10.1084/jem.180.4.1263",
      "article-title": "Activation of human dendritic cells through CD40 cross-linking",
      "volume": "180",
      "author": "Caux",
      "year": "1994",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R10",
      "doi-asserted-by": "crossref",
      "first-page": "317",
      "DOI": "10.1084/jem.185.2.317",
      "article-title": "Maturation stages of mouse dendritic cells in growth factor\u2013dependent long-term cultures",
      "volume": "185",
      "author": "Winzler",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R11",
      "doi-asserted-by": "crossref",
      "first-page": "1849",
      "DOI": "10.1084/jem.180.5.1849",
      "article-title": "The tissue distribution of the B7-2 costimulator in miceabundant expression on dendritic cells in situ and during maturation in vitro",
      "volume": "180",
      "author": "Inaba",
      "year": "1994",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R12",
      "doi-asserted-by": "crossref",
      "first-page": "1841",
      "DOI": "10.1084/jem.180.5.1841",
      "article-title": "B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells",
      "volume": "180",
      "author": "Caux",
      "year": "1994",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R13",
      "doi-asserted-by": "crossref",
      "first-page": "747",
      "DOI": "10.1084/jem.184.2.747",
      "article-title": "Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacityT-T help via APC activation",
      "volume": "184",
      "author": "Cella",
      "year": "1996",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R14",
      "doi-asserted-by": "crossref",
      "first-page": "741",
      "DOI": "10.1084/jem.184.2.741",
      "article-title": "High level IL-12 production by murine dendritic cellsupregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10",
      "volume": "184",
      "author": "Koch",
      "year": "1996",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R15",
      "doi-asserted-by": "crossref",
      "first-page": "1",
      "DOI": "10.1016/S0022-1759(98)00208-7",
      "article-title": "Generation of large numbers of fully mature and stable dendritic cells from leukapheresis products for clinical application",
      "volume": "223",
      "author": "Thurner",
      "year": "1999",
      "journal-title": "J. Immunol. Methods."
    },
    {
      "key": "2023072509161712000_R16",
      "doi-asserted-by": "crossref",
      "first-page": "373",
      "DOI": "10.1084/jem.188.2.373",
      "article-title": "Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites",
      "volume": "188",
      "author": "Dieu",
      "year": "1998",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R17",
      "doi-asserted-by": "crossref",
      "first-page": "3096",
      "DOI": "10.4049/jimmunol.161.6.3096",
      "article-title": "EB11/CCR7 is a new member of dendritic cell chemokine receptor that is upregulated upon maturation",
      "volume": "161",
      "author": "Yanagihara",
      "year": "1998",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509161712000_R18",
      "doi-asserted-by": "crossref",
      "first-page": "2760",
      "DOI": "10.1002/(SICI)1521-4141(199809)28:09<2760::AID-IMMU2760>3.0.CO;2-N",
      "article-title": "Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation",
      "volume": "28",
      "author": "Sallusto",
      "year": "1998",
      "journal-title": "Eur. J. Immunol."
    },
    {
      "key": "2023072509161712000_R19",
      "doi-asserted-by": "crossref",
      "first-page": "819",
      "DOI": "10.1126/science.284.5415.819",
      "article-title": "Chemokine up-regulation and activated T cell attraction by maturing dendritic cells",
      "volume": "284",
      "author": "Tang",
      "year": "1999",
      "journal-title": "Science."
    },
    {
      "key": "2023072509161712000_R20",
      "doi-asserted-by": "crossref",
      "first-page": "782",
      "DOI": "10.1038/42030",
      "article-title": "Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells",
      "volume": "388",
      "author": "Cella",
      "year": "1997",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509161712000_R21",
      "doi-asserted-by": "crossref",
      "first-page": "787",
      "DOI": "10.1038/42039",
      "article-title": "Developmental regulation of MHC class II transport in mouse dendritic cells",
      "volume": "388",
      "author": "Pierre",
      "year": "1997",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509161712000_R22",
      "doi-asserted-by": "crossref",
      "first-page": "1135",
      "DOI": "10.1016/S0092-8674(00)81458-0",
      "article-title": "Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells",
      "volume": "93",
      "author": "Pierre",
      "year": "1998",
      "journal-title": "Cell."
    },
    {
      "key": "2023072509161712000_R23",
      "doi-asserted-by": "crossref",
      "first-page": "615",
      "DOI": "10.1038/345615a0",
      "article-title": "Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding",
      "volume": "345",
      "author": "Roche",
      "year": "1990",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509161712000_R24",
      "doi-asserted-by": "crossref",
      "first-page": "1107",
      "DOI": "10.1084/jem.180.3.1107",
      "article-title": "The CLIP region of invariant chain plays a critical role in regulating major histocompatibility complex class II folding, transport, and peptide occupancy",
      "volume": "180",
      "author": "Romagnoli",
      "year": "1994",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R25",
      "doi-asserted-by": "crossref",
      "first-page": "13856",
      "DOI": "10.1073/pnas.94.25.13856",
      "article-title": "Production, specificity, and functionality of monoclonal antibodies to specific peptide-major histocompatibility complex class II complexes formed by processing of exogenous protein",
      "volume": "94",
      "author": "Zhong",
      "year": "1997",
      "journal-title": "Proc. Natl. Acad. Sci. USA"
    },
    {
      "key": "2023072509161712000_R26",
      "doi-asserted-by": "crossref",
      "first-page": "673",
      "DOI": "10.1084/jem.186.5.673",
      "article-title": "Antigen-unspecific B cells and lymphoid dendritic cells both show extensive surface expression of processed antigen\u2013major histocompatibility class II complexes after soluble protein exposure in vivo or in vitro",
      "volume": "186",
      "author": "Zhong",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R27",
      "doi-asserted-by": "crossref",
      "first-page": "1183",
      "DOI": "10.1084/jem.186.8.1183",
      "article-title": "Dendritic cells as adjuvants for immune-mediated resistance to tumors",
      "volume": "186",
      "author": "Schuler",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R28",
      "doi-asserted-by": "crossref",
      "first-page": "328",
      "DOI": "10.1038/nm0398-328",
      "article-title": "Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells",
      "volume": "4",
      "author": "Nestle",
      "year": "1998",
      "journal-title": "Nat. Med."
    },
    {
      "key": "2023072509161712000_R29",
      "doi-asserted-by": "crossref",
      "first-page": "173",
      "DOI": "10.1172/JCI6909",
      "article-title": "Rapid generation of broad T-cell immunity in humans after single injection of mature dendritic cells",
      "volume": "104",
      "author": "Dhodopkar",
      "year": "1999",
      "journal-title": "J. Clin. Invest."
    },
    {
      "key": "2023072509161712000_R30",
      "doi-asserted-by": "crossref",
      "first-page": "1669",
      "DOI": "10.1084/jem.190.11.1669",
      "article-title": "Vaccination with Mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma",
      "volume": "190",
      "author": "Thurner",
      "year": "1999",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R31",
      "doi-asserted-by": "crossref",
      "first-page": "1693",
      "DOI": "10.1084/jem.176.6.1693",
      "article-title": "Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor",
      "volume": "176",
      "author": "Inaba",
      "year": "1992",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R32",
      "doi-asserted-by": "crossref",
      "first-page": "1483",
      "DOI": "10.1084/jem.172.5.1483",
      "article-title": "Migration and maturation of Langerhans cells in skin transplants and explants",
      "volume": "172",
      "author": "Larsen",
      "year": "1990",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R33",
      "doi-asserted-by": "crossref",
      "first-page": "11",
      "DOI": "10.1111/1523-1747.ep12613452",
      "article-title": "Both dendritic cells and memory T lymphocytes emigrate from organ cultures of human skin and form distinctive dendritic-T-cell conjugates",
      "volume": "104",
      "author": "Pope",
      "year": "1995",
      "journal-title": "J. Invest. Dermatol."
    },
    {
      "key": "2023072509161712000_R34",
      "doi-asserted-by": "crossref",
      "first-page": "261",
      "DOI": "10.1093/oxfordjournals.jbchem.a123191",
      "article-title": "Tachyplesins isolated from hemocytes of Southeast Asian horseshoe crabs (Carcinoscorpius rotundicauda and Tachypleus gigas)identification of a new tachyplesin, tachyplesin III, and a processing intermediate of its precursor",
      "volume": "108",
      "author": "Muta",
      "year": "1990",
      "journal-title": "J. Biochem."
    },
    {
      "key": "2023072509161712000_R35",
      "doi-asserted-by": "crossref",
      "first-page": "1539",
      "DOI": "10.1084/jem.179.5.1539",
      "article-title": "Resting and anergic B cells are defective in CD28-dependent costimulation of naive CD4+ T cells",
      "volume": "179",
      "author": "Ho",
      "year": "1994",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R36",
      "doi-asserted-by": "crossref",
      "first-page": "6552",
      "DOI": "10.4049/jimmunol.162.11.6552",
      "article-title": "Analysis of adjuvant function by direct visualization of antigen presentation in vivoendotoxin promotes accumulation of antigen-bearing dendritic cells in the T cell areas of lymphoid tissue",
      "volume": "162",
      "author": "Reis e Sousa",
      "year": "1999",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509161712000_R37",
      "article-title": "Transport of peptide-MHC class II complexes in developing dendritic cells",
      "volume": "In press",
      "author": "Turley",
      "year": "2000",
      "journal-title": "Science"
    },
    {
      "key": "2023072509161712000_R38",
      "doi-asserted-by": "crossref",
      "first-page": "71",
      "DOI": "10.1016/0022-1759(96)00058-0",
      "article-title": "An improved isolation method for murine migratory cutaneous dendritic cells",
      "volume": "193",
      "author": "Ortner",
      "year": "1996",
      "journal-title": "J. Immunol. Methods."
    },
    {
      "key": "2023072509161712000_R39",
      "doi-asserted-by": "crossref",
      "first-page": "441",
      "DOI": "10.1046/j.1523-1747.1998.00161.x",
      "article-title": "Entry into afferent lymphatics and maturation in situ of migrating murine cutaneous dendritic cells",
      "volume": "110",
      "author": "Weinlich",
      "year": "1998",
      "journal-title": "J. Invest. Dermatol."
    },
    {
      "key": "2023072509161712000_R40",
      "doi-asserted-by": "crossref",
      "first-page": "641",
      "DOI": "10.1084/jem.185.4.641",
      "article-title": "Requirements for peptide-induced T cell receptor downregulation on naive CD8+ T cells",
      "volume": "185",
      "author": "Cai",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R41",
      "doi-asserted-by": "crossref",
      "first-page": "89",
      "DOI": "10.1016/S1074-7613(00)80461-6",
      "article-title": "The duration of antigenic stimulation determines the fate of naive and effector T cells",
      "volume": "8",
      "author": "Iezzi",
      "year": "1998",
      "journal-title": "Immunity."
    },
    {
      "key": "2023072509161712000_R42",
      "doi-asserted-by": "crossref",
      "first-page": "2025",
      "DOI": "10.1002/(SICI)1521-4141(199806)28:06<2025::AID-IMMU2025>3.0.CO;2-C",
      "article-title": "The chemokine SLC is expressed in T cell areas of lymph nodes amd mucosal lymphoid tissues and attracts activated T cells via CCR7",
      "volume": "28",
      "author": "Willimann",
      "year": "1998",
      "journal-title": "Eur. J. Immunol."
    },
    {
      "key": "2023072509161712000_R43",
      "doi-asserted-by": "crossref",
      "first-page": "451",
      "DOI": "10.1084/jem.189.3.451",
      "article-title": "Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization",
      "volume": "189",
      "author": "Gunn",
      "year": "1999",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R44",
      "doi-asserted-by": "crossref",
      "first-page": "267",
      "DOI": "10.1146/annurev.cb.11.110195.001411",
      "article-title": "How MHC class II molecules acquire peptide cargobiosynthesis and trafficking through the endocytic pathway",
      "volume": "11",
      "author": "Wolf",
      "year": "1995",
      "journal-title": "Annu. Rev. Cell Dev. Biol."
    },
    {
      "key": "2023072509161712000_R45",
      "doi-asserted-by": "crossref",
      "first-page": "821",
      "DOI": "10.1146/annurev.immunol.15.1.821",
      "article-title": "Capture and processing of exogenous antigens for presentation on MHC molecules",
      "volume": "15",
      "author": "Watts",
      "year": "1997",
      "journal-title": "Annu. Rev. Immunol."
    },
    {
      "key": "2023072509161712000_R46",
      "doi-asserted-by": "crossref",
      "first-page": "707",
      "DOI": "10.1016/0092-8674(90)90137-4",
      "article-title": "MHC class II-associated invariant chain contains a sorting signal for endosomal compartments",
      "volume": "63",
      "author": "Bakke",
      "year": "1990",
      "journal-title": "Cell."
    },
    {
      "key": "2023072509161712000_R47",
      "doi-asserted-by": "crossref",
      "first-page": "681",
      "DOI": "10.1084/jem.179.2.681",
      "article-title": "The invariant chain is required for intracellular transport and function of major histocompatibility complex class II molecules",
      "volume": "179",
      "author": "Elliot",
      "year": "1994",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R48",
      "doi-asserted-by": "crossref",
      "first-page": "429",
      "DOI": "10.1084/jem.185.3.429",
      "article-title": "Related leucine-based cytoplasmic targeting signals in invariant chain and major histocompatibility complex class II molecules control endocytic presentation of distinct determinants in a single protein",
      "volume": "185",
      "author": "Zhong",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R49",
      "doi-asserted-by": "crossref",
      "first-page": "133",
      "DOI": "10.1038/343133a0",
      "article-title": "Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment",
      "volume": "343",
      "author": "Guagliardi",
      "year": "1990",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509161712000_R50",
      "doi-asserted-by": "crossref",
      "first-page": "120",
      "DOI": "10.1038/369120a0",
      "article-title": "Isolation and characterization of the intracellular MHC class II compartment",
      "volume": "369",
      "author": "Tulp",
      "year": "1994",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509161712000_R51",
      "doi-asserted-by": "crossref",
      "first-page": "113",
      "DOI": "10.1038/369113a0",
      "article-title": "Transient accumulation of new class II MHC molecules in a novel endocytic compartment in B lymphocytes",
      "volume": "369",
      "author": "Amigorena",
      "year": "1994",
      "journal-title": "Nature"
    },
    {
      "key": "2023072509161712000_R52",
      "doi-asserted-by": "crossref",
      "first-page": "1566",
      "DOI": "10.1126/science.7985027",
      "article-title": "Accumulation of HLA-DM, a regulator of antigen presentation, in MHC class II compartments",
      "volume": "266",
      "author": "Sanderson",
      "year": "1994",
      "journal-title": "Science."
    },
    {
      "key": "2023072509161712000_R53",
      "doi-asserted-by": "crossref",
      "first-page": "229",
      "DOI": "10.1016/S1074-7613(00)80431-8",
      "article-title": "HLA-DM is localized to conventional and unconventional MHC class II-containing endocytic compartments",
      "volume": "4",
      "author": "Pierre",
      "year": "1996",
      "journal-title": "Immunity."
    },
    {
      "key": "2023072509161712000_R54",
      "doi-asserted-by": "crossref",
      "first-page": "389",
      "DOI": "10.1084/jem.182.2.389",
      "article-title": "Dendritic cells use macropinocytosis and the mannose receptor to concentrate antigen in the major histocompatibility class II compartment. Downregulation by cytokines and bacterial products",
      "volume": "182",
      "author": "Sallusto",
      "year": "1995",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R55",
      "doi-asserted-by": "crossref",
      "first-page": "163",
      "DOI": "10.1084/jem.182.1.163",
      "article-title": "Antigen capture and MHC class II compartments of freshly isolated and cultured human blood dendritic cells",
      "volume": "182",
      "author": "Nijman",
      "year": "1995",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R56",
      "doi-asserted-by": "crossref",
      "first-page": "357",
      "DOI": "10.1016/S1074-7613(00)80249-6",
      "article-title": "Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading",
      "volume": "4",
      "author": "Riese",
      "year": "1996",
      "journal-title": "Immunity."
    },
    {
      "key": "2023072509161712000_R57",
      "doi-asserted-by": "crossref",
      "first-page": "1349",
      "DOI": "10.1126/science.2113314",
      "article-title": "A cell culture model for T lymphocyte clonal anergy",
      "volume": "248",
      "author": "Schwartz",
      "year": "1990",
      "journal-title": "Science"
    },
    {
      "key": "2023072509161712000_R58",
      "doi-asserted-by": "crossref",
      "first-page": "1753",
      "DOI": "10.1084/jem.178.5.1753",
      "article-title": "B7 but not intercellular adhesion molecule-1 costimulation prevents the induction of human alloantigen\u2013specific tolerance",
      "volume": "178",
      "author": "Boussiotis",
      "year": "1993",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R59",
      "doi-asserted-by": "crossref",
      "first-page": "2163",
      "DOI": "10.1084/jem.188.11.2163",
      "article-title": "Efficient presentation of phagocytosed cellular fragments on the MHC class II products of dendritic cells",
      "volume": "188",
      "author": "Inaba",
      "year": "1998",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R60",
      "doi-asserted-by": "crossref",
      "first-page": "239",
      "DOI": "10.1084/jem.186.2.239",
      "article-title": "Class I\u2013restricted cross-presentation of exogenous self-antigens leads to deletion of autoreactive CD8+ T cells",
      "volume": "186",
      "author": "Kurts",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509161712000_R61",
      "doi-asserted-by": "crossref",
      "first-page": "665",
      "DOI": "10.1084/jem.186.5.665",
      "article-title": "High levels of a major histocompatibility complex II\u2013self-peptide complex on dendritic cells from the T cell areas of lymph nodes",
      "volume": "186",
      "author": "Inaba",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    }
  ],
  "container-title": "The Journal of Experimental Medicine",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://rupress.org/jem/article-pdf/191/6/927/1698424/000019.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://rupress.org/jem/article-pdf/191/6/927/1698424/000019.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        7,
        25
      ]
    ],
    "date-time": "2023-07-25T10:31:14Z",
    "timestamp": 1690281074000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://rupress.org/jem/article/191/6/927/20243/The-Formation-of-Immunogenic-Major"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2000,
        3,
        13
      ]
    ]
  },
  "references-count": 61,
  "journal-issue": {
    "issue": "6",
    "published-print": {
      "date-parts": [
        [
          2000,
          3,
          20
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1084/jem.191.6.927",
  "relation": {},
  "ISSN": [
    "0022-1007",
    "1540-9538"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2000,
        3,
        13
      ]
    ]
  }
}