DOI: 10.1084/jem.186.7.1149. How Many Thymocytes Audition for Selection?

How Many Thymocytes Audition for Selection?

10.1084/jem.186.7.1149

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

T cell maturation requires the rearrangement of clonotypic T cell receptors (TCR) capable of interacting with major histocompatibility complex (MHC) ligands to initiate positive and negative selection. Only 3–5% of thymocytes mature to join the peripheral T cell pool. To investigate the basis for this low success rate, we have measured the frequency of preselection thymocytes capable of responding to MHC. As many as one in five MHC-naive thymocytes show upregulation of activation markers on exposure to MHC-expressing thymic stroma in short-term reaggregate culture. The majority of these cells display physiological changes consistent with entry into the selection process within 24 h. By exposing TCR transgenic thymocytes to a range of MHC–peptide complexes, we show that CD69 induction is indicative of thymocyte selection, positive or negative. Our data provide evidence that the fraction of thymocytes that qualify to enter the thymic selection process far exceeds the fraction that successfully complete it, and suggest that most MHC-reactive thymocytes are actively eliminated in the course of selection.

Bibliography

Merkenschlager, M., Graf, D., Lovatt, M., Bommhardt, U., Zamoyska, R., & Fisher, A. G. (1997). How Many Thymocytes Audition for Selection? The Journal of Experimental Medicine, 186(7), 1149â1158.

Authors 6

Matthias Merkenschlager (first)
Daniel Graf (additional)
Matthew Lovatt (additional)
Ursula Bommhardt (additional)
Rose Zamoyska (additional)
Amanda G. Fisher (additional)

References 57 Referenced 177

10.1016/S0065-2776(08)60262-X / Adv Immunol / MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness by Zinkernagel (1979)
10.1038/269417a0 / Nature (Lond) / In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells by Bevan (1977)
10.1146/annurev.iy.10.040192.004155 / Annu Rev Immunol / Molecular components of T-cell recognition by Jorgensen (1992)
10.1016/S0065-2776(08)60620-3 / Adv Immunol / Development and selection of T cells: facts and puzzles by Kisielow (1995)
10.1111/j.1600-065X.1995.tb00099.x / Immunol Rev / Mice lacking terminal deoxynucleotidyl transferase: adult mice with a fetal antigen receptor repertoire by Gilfillan (1995)
10.1038/372100a0 / Nature (Lond) / T-cell apoptosis detected in situ during positive and negative selection in the thymus by Surh (1994)
10.1084/jem.173.2.323 / J Exp Med / The kinetics of T cell antigen receptor expression by subgroups of CD4+8+thymocytes: delineation of CD4+8+3(2+) thymocytes as post-selection intermediates leading to mature T cells by Shortman (1991)
10.1016/0092-8674(81)90016-7 / Cell / Kinetics and efficacy of positive selection in the thymus of normal and T cell receptor transgenic mice by Huesmann (1991)
10.1002/eji.1830230829 / Eur J Immunol / Regulation of T cell production in T cell receptor transgenic mice by Kelly (1993)
10.1073/pnas.91.24.11694 / Proc Natl Acad Sci USA / Evidence for a single niche model of positive selection by Merkenschlager (1994)
10.1146/annurev.iy.13.040195.000521 / Annu Rev Immunol / Positive selection of thymocytes by Jameson (1995)
10.1073/pnas.93.25.14747 / Proc Natl Acad Sci USA / Tuning of activation thresholds explains flexibility in the selection and development of T cells in the thymus by Grossman (1996)
10.1016/0092-8674(93)90225-F / Cell / Another view of the selective model of thymocyte selection by Chan (1993)
10.1038/383081a0 / Nature (Lond) / Unopposed positive selection and autoreactivity in mice expressing class II MHC only on thymic cortex by Laufer (1996)
10.1084/jem.185.3.377 / J Exp Med / Quantitative impact of thymic clonal deletion on the T cell repertoire by van Meerwijk (1997)
10.1002/eji.1830010102 / Eur J Immunol / The somatic generation of immune regulation by Jerne (1971)
10.1111/j.1600-065X.1993.tb00645.x / Immunol Rev / Why positive selection? by Matzinger (1993)
10.1016/0092-8674(86)90591-X / Cell / The T cell repertoire may be biased in favor of MHC recognition by Blackman (1986)
10.1016/S0092-8674(00)81029-6 / Cell / Mice lacking H2-M complexes, enigmatic elements of the MHC class II peptide-loading pathway by Miyazaki (1996)
10.1016/S0092-8674(00)81030-2 / Cell / H2-M mutant mice are defective in the peptide loading of class II molecules, antigen presentation, and T cell repertoire selection by Martin (1996)
10.1126/science.271.5253.1278 / Science (Wash DC) / Antigen presentation and T cell development in H2-M–deficient mice by Fung-Leung (1996)
10.1016/S0092-8674(00)81028-4 / Cell / The repertoire of T cells shaped by a single MHC/peptide ligand by Ignatowicz (1996)
10.1007/s002510050212 / Immunogenetics / The helper T cell repertoire of mice expressing class II major histocompatibility complex beta chains in the absence of alpha chains by Vidovic (1997)
10.1016/S0092-8674(00)81905-4 / Cell / The MHC reactivity of the T cell receptor repertoire prior to positive and negative selection by Zerrahn (1997)
10.1038/351482a0 / Nature (Lond) / Lower receptor avidity required for thymic clonal deletion than for effector T-cell function by Pircher (1991)
10.1084/jem.183.3.1093 / J Exp Med / Mature T cell reactivity altered by peptide agonist that induces positive selection by Sebzda (1996)
10.1016/0092-8674(94)90505-3 / Cell / Evidence for a differential avidity model of T cell selection in the thymus by Ashton-Rickardt (1994)
10.1016/0092-8674(94)90169-4 / Cell / T cell antagonist peptides induce positive selection by Hogquist (1994)
10.1084/jem.176.3.845 / J Exp Med / Studies on T cell maturation on defined thymic stromal cell populations in vitro by Jenkinson (1992)
10.4049/jimmunol.153.5.1915 / J Immunol / Characteristics of an in vitro system of thymocyte positive selection by Anderson (1994)
10.1084/jem.179.2.709 / J Exp Med / Negative selection of CD4+CD8+thymocytes by T cell receptor–induced apoptosis requires a costimulatory signal that can be provided by CD28 by Punt (1994)
10.1016/1074-7613(95)90056-X / Immunity / Receptors and signals in early thymic selection by Levelt (1995)
10.1084/jem.182.2.367 / J Exp Med / Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death by Zamzami (1995)
10.4049/jimmunol.148.5.1547 / J Immunol / Formation of a bispecific antibody by the use of leucine zippers by Kostelny (1992)
10.1002/eji.1830270516 / Eur J Immunol / Signals through CD4 or CD8 can induce commitment to the CD4 lineage in the thymus by Bommhardt (1997)
10.1002/eji.1830181102 / Eur J Immunol / Limiting dilution analysis of proliferative responses in human lymphocyte populations defined by the monoclonal antibody UCHL1: implications for differential CD45 expression in T cell memory formation by Merkenschlager (1988)
10.4049/jimmunol.143.6.1822 / J Immunol / Two better cell lines for making hybridomas expressing specific T cell receptors by White (1989)
10.1084/jem.175.3.731 / J Exp Med / Activation events during thymic selection by Bendelac (1992)
10.1002/eji.1830240122 / Eur J Immunol / Regulation of RAG-1 and CD69 expression in the thymus during positive and negative selection by Brändle (1994)
10.1016/1074-7613(95)90061-6 / Immunity / Localization, interaction, and RNA binding properties of the V(D)J recombination-activating proteins RAG1 and RAG2 by Spanopoulou (1995)
10.1126/science.2112266 / Science (Wash DC) / Normal development of mice deficient in beta 2m, MHC class I proteins, and CD8+T cells by Koller (1990)
10.1016/S1074-7613(00)80282-4 / Immunity / Identification of a naturally occurring ligand for positive selection by Hogquist (1997)
10.1084/jem.177.6.1541 / J Exp Med / Clone-specific T cell receptor antagonists of major histocompatibility complex class I–restricted cytotoxic T cells by Jameson (1993)
10.1038/369750a0 / Nature (Lond) / Specificity and flexibility in thymic selection by Jameson (1994)
10.1038/381616a0 / Nature (Lond) / T-cell–receptor affinity and thymocyte positive selection by Alam (1996)
10.4049/jimmunol.154.6.2588 / J Immunol / Distinct differentiative stages of CD4+CD8+thymocyte development defined by the lack of coreceptor binding in positive selection by Dutz (1995)
10.1016/S1074-7613(00)80502-6 / Immunity / Unexpectedly complex regulation of CD4/CD8 coreceptor expression supports a revised model for CD4+CD8+thymocyte differentiation by Lucas (1996)
10.1016/S1074-7613(00)80327-1 / Immunity / Surface molecules that drive T cell development in vitro in the absence of thymic epithelium and in the absence of lineage specific signals by Cibotti (1997)
10.1084/jem.181.2.649 / J Exp Med / Upregulation of surface markers on dying thymocytes by Kishimoto (1995)
10.1002/eji.1830230740 / Eur J Immunol / T cell receptor targeting to thymic cortical epithelial cells in vivo induces survival, activation and differentiation of immature thymocytes by Müller (1993)
10.1038/371067a0 / Nature (Lond) / Positive selection of CD4+ T cells by TCR ligation without aggregation even in the absence of MHC by Takahama (1994)
10.1084/jem.184.5.1747 / J Exp Med / Invariant chain and DM edit self-peptide presentation by major histocompatibility complex (MHC) class II molecules by Katz (1996)
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10.1038/334395a0 / Nature (Lond) / T-cell antigen receptor genes and T-cell recognition by Davis (1988)
10.1016/S1074-7613(00)80250-2 / Immunity / The specificity and orientation of a TCR to its peptide–MHC class II ligands by Sant'Angelo (1996)
10.1038/384134a0 / Nature (Lond) / Structure of the complex between human T cell receptor, viral peptide and HLA A2 by Garboczi (1996)
10.1126/science.274.5285.209 / Science (Wash DC) / An alpha beta T cell receptor structure at 2.5 Å and its orientation in the TCR–MHC complex by Garcia (1996)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:49 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 4:23 a.m.)
Indexed	1 month, 1 week ago (July 23, 2025, 9:03 a.m.)
Issued	27 years, 10 months ago (Oct. 6, 1997)
Published	27 years, 10 months ago (Oct. 6, 1997)
Published Online	27 years, 10 months ago (Oct. 6, 1997)
Published Print	27 years, 10 months ago (Oct. 6, 1997)

Funders 0

None

BibTeX

@article{Merkenschlager_1997, title={How Many Thymocytes Audition for Selection?}, volume={186}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.186.7.1149}, DOI={10.1084/jem.186.7.1149}, number={7}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Merkenschlager, Matthias and Graf, Daniel and Lovatt, Matthew and Bommhardt, Ursula and Zamoyska, Rose and Fisher, Amanda G.}, year={1997}, month=oct, pages={1149–1158} }

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      "first-page": "417",
      "DOI": "10.1038/269417a0",
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      "volume": "269",
      "author": "Bevan",
      "year": "1977",
      "journal-title": "Nature (Lond)"
    },
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      "key": "2023072507392152600_B3",
      "doi-asserted-by": "crossref",
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      "DOI": "10.1146/annurev.iy.10.040192.004155",
      "article-title": "Molecular components of T-cell recognition",
      "volume": "10",
      "author": "Jorgensen",
      "year": "1992",
      "journal-title": "Annu Rev Immunol"
    },
    {
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      "first-page": "87",
      "DOI": "10.1016/S0065-2776(08)60620-3",
      "article-title": "Development and selection of T cells: facts and puzzles",
      "volume": "58",
      "author": "Kisielow",
      "year": "1995",
      "journal-title": "Adv Immunol"
    },
    {
      "key": "2023072507392152600_B5",
      "doi-asserted-by": "crossref",
      "first-page": "201",
      "DOI": "10.1111/j.1600-065X.1995.tb00099.x",
      "article-title": "Mice lacking terminal deoxynucleotidyl transferase: adult mice with a fetal antigen receptor repertoire",
      "volume": "148",
      "author": "Gilfillan",
      "year": "1995",
      "journal-title": "Immunol Rev"
    },
    {
      "key": "2023072507392152600_B6",
      "doi-asserted-by": "crossref",
      "first-page": "100",
      "DOI": "10.1038/372100a0",
      "article-title": "T-cell apoptosis detected in situ during positive and negative selection in the thymus",
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      "author": "Surh",
      "year": "1994",
      "journal-title": "Nature (Lond)"
    },
    {
      "key": "2023072507392152600_B7",
      "doi-asserted-by": "crossref",
      "first-page": "323",
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      "author": "Shortman",
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      "author": "Kelly",
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      "volume": "47",
      "author": "Blackman",
      "year": "1986",
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      "volume": "84",
      "author": "Martin",
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      "first-page": "1278",
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      "volume": "271",
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      "volume": "84",
      "author": "Ignatowicz",
      "year": "1996",
      "journal-title": "Cell"
    },
    {
      "key": "2023072507392152600_B23",
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      "first-page": "325",
      "DOI": "10.1007/s002510050212",
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      "volume": "45",
      "author": "Vidovic",
      "year": "1997",
      "journal-title": "Immunogenetics"
    },
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