GENERATION OF ALLOSPECIFIC NATURAL-KILLER-CELLS BY STIMULATION ACROSSA POLYMORPHISM OF HLA-C

The cytotoxicity of human natural killer (NK) cells is modulated by th e major histocompatibility complex human leukocyte antigen (HLA)-C mol ecules on the surface of the target cell. Alloreactive NK cells specif ic for the NK-1 alloantigen could be reproducibly generated from indiv iduals that were homozygous for HLA-C with asparagine at residue 77 an d lysine at residue 80 [HLA-C(Asn77, Lys80] by stimulation with target cells that were homozygous for HLA-C(Ser77, Asn80); the reciprocal st imulation yielded NK cells specific for the NK-2 alloantigen. However, neither homozygous target cell stimulated the generation of alloreact ive NK cells from heterozygous individuals. Thus, these data reveal an unanticipated difference between human NK alloreactivity defined by t his system and murine ''hybrid resistance.''