DOI: 10.1084/jem.184.6.2119. The Ly-49D Receptor Activates Murine Natural Killer Cells

The Ly-49D Receptor Activates Murine Natural Killer Cells

10.1084/jem.184.6.2119

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

Proteins encoded by members of the Ly-49 gene family are predominantly expressed on murine natural killer (NK) cells. Several members of this gene family have been demonstrated to inhibit NK cell lysis upon recognizing their class I ligands on target cells. In this report, we present data supporting that not all Ly-49 proteins inhibit NK cell function. Our laboratory has generated and characterized a monoclonal antibody (mAb) (12A8) that can be used to recognize the Ly-49D subset of murine NK cells. Transfection of Cos-7 cells with known members of the Ly-49 gene family revealed that 12A8 recognizes Ly-49D, but also cross-reacts with the Ly-49A protein on B6 NK cells. In addition, 12A8 demonstrates reactivity by both immunoprecipitation and two-color flow cytometry analysis with an NK cell subset that is distinct from those expressing Ly-49A, C, or G2. An Ly-49D+ subset of NK cells that did not express Ly49A, C, and G2 was isolated and examined for their functional capabilities. Tumor targets and concanovalin A (ConA) lymphoblasts from a variety of H2 haplotypes were examined for their susceptibility to lysis by Ly-49D+ NK cells. None of the major histocompatibility complex class I–bearing targets inhibited lysis of Ly-49D+ NK cells. More importantly, we demonstrate that the addition of mAb 12A8 to Ly-49D+ NK cells can augment lysis of FcγR+ target cells in a reverse antibody-dependent cellular cytotoxicity–type assay and induces apoptosis in Ly49D+ NK cells. Furthermore, the cytoplasmic domain of Ly-49D does not contain the V/IxYxxL immunoreceptor tyrosine-based inhibitory motif found in Ly-49A, C, or G2 that has been characterized in the human p58 killer inhibitory receptors. Therefore, Ly-49D is the first member of the Ly-49 family characterized as transmitting positive signals to NK cells, rather than inhibiting NK cell function.

Bibliography

Mason, L. H., Anderson, S. K., Yokoyama, W. M., Smith, H. R. C., Winkler-Pickett, R., & Ortaldo, J. R. (1996). The Ly-49D Receptor Activates Murine Natural Killer Cells. The Journal of Experimental Medicine, 184(6), 2119â2128.

Authors 6

L.H. Mason (first)
S.K. Anderson (additional)
W.M. Yokoyama (additional)
H.R.C. Smith (additional)
R. Winkler-Pickett (additional)
J.R. Ortaldo (additional)

References 24 Referenced 155

10.1016/0167-5699(90)90097-S / Immunol Today / In search of the “missing self ”: MHC molecules and NK cell recognition by Ljunggren (1990)
10.4049/jimmunol.147.4.1417 / J Immunol / Ly-49 multigene family. New members of a superfamily of type II-membrane proteins with lectin-like domains by Wong (1991)
10.4049/jimmunol.153.3.1068 / J Immunol / Ly-49 multigene family expressed by IL-2 activated NK cells by Smith (1994)
10.1038/358066a0 / Nature (Lond) / MHC class I alloantigen specificity of Ly-49+IL-2 activated natural killer cells by Karlhofer (1992)
10.1084/jem.179.3.1011 / J Exp Med / Ly-49 mediates EL4 lymphoma adhesion to isolated class I major histocompatibility complex molecules by Kane (1994)
10.4049/jimmunol.145.7.2353 / J Immunol / Chromosomal localization of the Ly-49 (A1, YE1/48) multigene family. Genetic association with the NK1.1 antigen by Yokoyama (1990)
{'key': '2023072819531072500_B7', 'first-page': '789', 'article-title': 'Ly-49A, a receptor for H-2Dd, has a functional carbohydrate recognition domain', 'volume': '1', 'author': 'Daniel', 'year': '1994', 'journal-title': 'Immunity'} / Immunity / Ly-49A, a receptor for H-2Dd, has a functional carbohydrate recognition domain by Daniel (1994)
10.1084/jem.182.2.293 / J Exp Med / Cloning and functional characteristics of murine large granular lymphocyte-1: a member of the Ly-49 gene family (Ly-49G2) by Mason (1995)
10.1084/jem.180.6.2287 / J Exp Med / Expression of different members of the Ly-49 gene family define distinct natural killer cell subsets and cell adhesion properties by Brennan (1994)
10.1016/S1074-7613(00)80299-X / Immunity / The role of Ly-49A and 5E6 (Ly49C) molecules in hybrid resistance mediated by murine natural killer cells against normal T cell blasts by Yu (1996)
10.1084/jem.170.1.191 / J Exp Med / Identification of a subset of murine natural killer cells that mediates rejection of Hh-1d but not Hh-1bbone marrow grafts by Sentman (1989)
10.4049/jimmunol.155.6.2911 / J Immunol / NK cell subsets in the regulation of murine hematopoiesis. I. 5E6+ NK cells promote hematopoietic growth in H-2dstrain mice by Murphy (1995)
10.4049/jimmunol.140.12.4403 / J Immunol / LGL-1: a non-polymorphic antigen expressed on a major population of mouse natural killer cells by Mason (1988)
10.4049/jimmunol.148.7.2307 / J Immunol / Hybrid resistance in vitro. Possible role of both class I MHC and self peptides in determining the level of target cell sensitivity by Chadwick (1992)
{'key': '2023072819531072500_B15'}
{'key': '2023072819531072500_B15a'}
10.4049/jimmunol.143.4.1379 / J Immunol / A murine T lymphocyte antigen belongs to a supergene family of type II integral membrane proteins by Yokoyama (1989)
10.4049/jimmunol.146.10.3662 / J Immunol / Stimulation of murine natural killer (NK) cells by a monoclonal antibody specific for the NK-1.1 antigen. IL-2 activated NK cells possess additional specific stimulation pathways by Karlhofer (1991)
10.4049/jimmunol.145.2.751 / J Immunol / Natural killer (NK) cell subsets in the mouse: NK-1.1+/LGL-1+ cells restricted to lysing NK targets, whereas NK-1.1+/LGL-1−cells generate lymphokine-activated killer cells by Mason (1990)
10.1084/jem.182.2.305 / J Exp Med / Cloning and characterization of 5E6 (Ly49C), a receptor molecule expressed on a subset of murine natural killer cells by Stoneman (1995)
10.1038/353858a0 / Nature (Lond) / Interleukin-2 programs mouse alpha beta T lymphocytes for apoptosis by Lenardo (1991)
10.1126/science.7509084 / Science (Wash DC) / T cell deletion in high antigen dose therapy of autoimmune encephalomyelitis by Critchfield (1994)
10.1084/jem.181.1.339 / J Exp Med / Receptorinduced death in human natural killer cells: involvement of CD16 by Ortaldo (1995)
10.1016/S1074-7613(00)80300-3 / Immunity / Recruitment of tyrosine phosphatase HCP by the killer cell inhibitor receptor by Burshtyn (1996)

Dates

Type	When
Created	21 years, 2 months ago (June 24, 2004, 3:56 a.m.)
Deposited	2 years, 1 month ago (July 28, 2023, 3:53 p.m.)
Indexed	4 months, 4 weeks ago (March 31, 2025, 10:24 a.m.)
Issued	28 years, 8 months ago (Dec. 1, 1996)
Published	28 years, 8 months ago (Dec. 1, 1996)
Published Online	28 years, 8 months ago (Dec. 1, 1996)
Published Print	28 years, 8 months ago (Dec. 1, 1996)

Funders 0

None

BibTeX

@article{Mason_1996, title={The Ly-49D Receptor Activates Murine Natural Killer Cells}, volume={184}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.184.6.2119}, DOI={10.1084/jem.184.6.2119}, number={6}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Mason, L.H. and Anderson, S.K. and Yokoyama, W.M. and Smith, H.R.C. and Winkler-Pickett, R. and Ortaldo, J.R.}, year={1996}, month=dec, pages={2119–2128} }

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