Natural killer cell acceptance of H-2 mismatch bone marrow grafts in transgenic mice expressing HLA-Cw3 specific killer cell inhibitory receptor.
Natural killer (NK) cells express killer cell inhibitory receptors (KIRs) for major histocompatibility complex class I molecules. Engagement of these surface receptors inhibits NK cell cytotoxic programs. KIR can also be expressed on T cell subsets, and their engagement similarly results in inhibition of effector functions initiated by the CD3/T cell receptor complex. KIR genes belong to two distinct families: the immunoglobulin superfamily (IgSF KIRs) and dimeric C2 lectins (lectin-like KIRs). Whereas both IgSF (p58: CD158, p70, and p140) and lectin-like KIRs (CD94/NKG2A heterodimers) have been found in human, only lectin-like KIRs (all members of the Ly-49 family) have been described in the mouse. We have generated transgenic mice expressing an IgSF KIR, CD158b (p58.2), which recognizes HLA-Cw3. Our data show that CD158b is necessary and sufficient to confer specificity to NK cells, as well as to modulate T cell activation programs in vitro. In addition, we did not detect any adaptation of CD158b cell surface expression to that of HLA class I ligands in the CD158b x HLA-Cw3 double transgenic mice, in contrast to observations with Ly-49 in the mouse. Therefore, distinct strategies of selection/calibration appear to be used by IgSF and lectin-like KIRs. Finally, the transgenic expression of CD158b KIR prevents the in vivo rejection of H-2 mismatch bone marrow grafts, which express the cognate major histocompatibility class I HLA-Cw3 allele, demonstrating for the first time the in vivo implication of human IgSF KIRs in the negative regulation of NK cell function.
Cambiaggi
A
A
Centre d'Immunologie Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique de Marseille-Luminy, Case 906, 13288 Marseille cedex 09, France.
Verthuy
C
C
Naquet
P
P
Romagné
F
F
Ferrier
P
P
Biassoni
R
R
Moretta
A
A
Moretta
L
L
Vivier
E
E
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; D011971:Receptors, Immunologic