IDENTIFICATION OF AN INHIBITORY MHC RECEPTOR ON ALLOREACTIVE RAT NATURAL-KILLER-CELLS

Studies of allogeneic lymphocyte cytotoxicity have shown that the rat NK allorecognition repertoire is controlled by genetic elements in bot h the MHC (RT1) and the NK gene complex (NKC). DA rats, possessing NK cells that are unable to lyse allogeneic lymphoblasts, were immunized with alloreactive NK cells from MHC-matched PVG.1AV1 rats, and two mAb , STOK1 and STOK2, were generated, STOK1 and STOK2 stained identical s ubsets of NKR-P1(+) T and NK cells from certain strains of rats. Relat ive numbers varied markedly in a panel of MHC congenic strains, howeve r, implicating a role for self MHC genes in their development. Both ST OK1 and STOK2 immunoprecipitated a 110-kDa disulfide-linked homodimeri c molecule, with extensive N-linked glycosylations, encoded by a gene that mapped to the NKC. NK cells expressing this glycoprotein displaye d an increased ability to lyse allogeneic lymphoblasts, while syngenei c targets were spared, However, blockade of the STOK2 Ag with F(ab')(2 ) of STOK2 permitted the NK lysis of syngeneic targets, but did not af fect NK allorecognition. These results indicate that mAb STOK1 and STO K2 identify an NKC-encoded MHC receptor in the rat that acts as a nega tive regulator of cytotoxicity.