Regulation of T cell lymphokine production by killer cell inhibitory receptor recognition of self HLA class I alleles.
The killer cell inhibitory receptors (KIRs) are surface glycoproteins expressed by natural killer (NK) and T cells that specifically recognize defined groups of polymorphic human histocompatibility leukocyte antigen (HLA) class I molecules. Interactions between KIRs on NK or T cells and major histocompatibility complex (MHC) class I molecules on potential target cells inhibit cell-mediated cytotoxicity, presumably by delivering a negative signal preventing lymphocyte activation. In this study we examined whether KIRs also regulate cytokine production induced in response to T cell receptor-dependent T cell activation. CD4+ and CD8+ T cell clones were stimulated by bacterial superantigens in the presence or absence of monoclonal antibodies (mAbs) against the KIR NKB1 or MHC class I molecules, and production of tumor necrosis factor alpha and interferon gamma was evaluated. When bacterial superantigen was presented by an autologous antigen-presenting cell (APC) to a KIR+ T cell clone, cytokine production was always enhanced in the presence of anti-MHC class I mAb. Similarly, anti-KIR mAb also augmented cytokine production, provided that the APC expressed a HLA class I allele recognized by the KIR. These results suggest that recognition of autologous MHC class I molecules by KIR+ T cells provides a regulatory mechanism acting to modulate the potency of their responses to antigenic challenge.
D'Andrea
A
A
Department of Human Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Chang
C
C
Phillips
J H
JH
Lanier
L L
LL
D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D011971:Receptors, Immunologic / Q000276:immunology* / Q000502:physiology*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D018089:Superantigens; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004768:Enterotoxins; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma