Cutting Edge: KIR3DS1, a gene implicated in resistance to progression to AIDS, encodes a DAP12-associated receptor expressed on NK cells that triggers NK cell activation.
The killer cell Ig-like receptor (KIR) gene, KIR3DS1, has been implicated in slowing disease progression in HIV infection; however, little is known about its expression, function, or ligand specificity. Using retrovirally transduced NKL cells and peripheral blood NK cells from KIR3DS1-positive donors we assessed expression of this gene by flow cytometry and its function by in vitro assays measuring KIR3DS1-induced cell-mediated cytotoxicity and cytokine production. In the present study, we demonstrate that KIR3DS1 is expressed on peripheral blood NK cells and triggers both cytotoxicity and IFN-gamma production. Using cotransfection and coimmunoprecipitation, we found that KIR3DS1 associates with the ITAM-bearing adaptor, DAP12. Soluble KIR3DS1-Ig fusion proteins did not bind to EBV-transformed B lymphoid cell lines transfected with HLA-Bw4 80I or 80T allotypes, suggesting that if KIR3DS1 does recognize HLA-Bw4 ligands, this may be peptide dependent.
Carr
William H
WH
Department of Microbiology and Immunology, Cancer Research Institute and Biomedical Sciences Graduate Program, University of California-San Francisco, CA 94143, USA. wcarr@partners.org
Rosen
David B
DB
Arase
Hisashi
H
Nixon
Douglas F
DF
Michaelsson
Jakob
J
Lanier
Lewis L
LL
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018450:Disease Progression; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins; D051379:Mice; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D054340:Receptors, KIR; D054349:Receptors, KIR3DS1; D012995:Solubility
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054349:Receptors, KIR3DS1; C110546:TYROBP protein, human; D007371:Interferon-gamma