The MHC class I molecule H-2D(P) inhibits murine NK cells via the inhibitory receptor Ly49A

MHC class I molecules strongly influence the phenotype and function of mous e NK cells. NK cell-mediated Iysis is prevented through the interaction of Ly49 receptors on the effector cell with appropriate MHC class I ligands on the target cell. In addition, host MHC class I molecules have been shown t o modulate the in vivo expression of Ly49 receptors, We have previously rep orted that H-2D(d) and H-2D(P) MHC class I molecules are able to protect (a t the target cell level)from NK cell-mediated lysis and alter the NK cell s pecificity (at the host level) in a similar manner, although,the mechanism behind this was not clear, In this study; we demonstrate that the expressio n of both H-2D(d) and H-2D(p) class I molecules in target cells leads to in hibition of B6 (H-2(b))-derived Ly49A(+) NK cells.; This inhibition could i n both cases be reversed by anti-Ly49A Abs. Cellular conjugate assays showe d that Ly49A-expressing cells indeed bind to cells expressing H-2DP.: The e xpression of Ly49A and Ly49G2 receptors on NK cells,vas down-regulated in H -2D(P)-transgenic (B6DP) mice compared,vith nontransgenic B6 mice. However, B6DP mice expressed significantly higher levels of Ly49A compared with H-2 D(d)-transgenic (D8) mice. We propose that both H-2Dd and H-2D(p) MHC class I molecules can act as ligands for Ly49A.