MHC class I-deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I-sufficient environment.
In MHC class I-deficient hosts, natural killer (NK) cells are hyporesponsive to cross-linking of activation receptors. Functional competence requires engagement of a self-major histocompatability complex (MHC) class I-specific inhibitory receptor, a process referred to as "licensing." We previously suggested that licensing is developmentally determined in the bone marrow. In this study, we find that unlicensed mature MHC class I-deficient splenic NK cells show gain-of-function and acquire a licensed phenotype after adoptive transfer into wild-type (WT) hosts. Transferred NK cells produce WT levels of interferon-γ after engagement of multiple activation receptors, and degranulate at levels equivalent to WT NK cells upon coincubation with target cells. Only NK cells expressing an inhibitory Ly49 receptor specific for a cognate host MHC class I molecule show this gain-of-function. Therefore, these findings, which may be relevant to clinical bone marrow transplantation, suggest that neither exposure to MHC class I ligands during NK development in the BM nor endogenous MHC class I expression by NK cells themselves is absolutely required for licensing.
Elliott
Julie M
JM
Division of Biology and Biomedical Sciences, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Wahle
Joseph A
JA
Yokoyama
Wayne M
WM
D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000096:biosynthesis / Q000276:immunology*; D014181:Transplantation Immunology
D015395:Histocompatibility Antigens Class I; D055650:NK Cell Lectin-Like Receptor Subfamily A; D007371:Interferon-gamma
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