The NK1.1 antigen in NK-mediated F1 antiparent killing in vitro

Abstract

NK cells in lethally irradiated F1(A x B) hybrid mice can reject parental A or B strain bone marrow cells, a phenomenon called "hybrid resistance." The recognition mechanism used by the NK cells remains unknown. Our laboratory has previously described an in vitro model for hybrid resistance, and we have used it here to test whether the NK surface marker, NK1.1, is involved in such recognition. We found that 1) an anti-NK1.1 mAb (PK136) inhibited F1 lymphokine-activated killer (LAK) antiparent lysis if the LAK expressed NK1.1. Other mAb, even a mAb such as 2B4 that recognizes the same LAK as PK136, did not produce inhibition. 2) The F(ab')2 fragment of PK136 also inhibited lysis. 3) F1 LAK generated from athymic nude mice were as effective antiparent killers as LAK from normal mice and were equally inhibitable by anti-NK1.1 mAb, strengthening the conclusion that killing is mediated by NK cells and not T cells. 4) As previously shown by others, addition of anti-NK1.1 mAb to a mixture of NK1.1+ LAK cells and NK-resistant FcR+ cells allowed lysis of the FcR+ cells via "redirected lysis," in which the anti-NK1.1 mAb binds to NK1.1 on the NK cells and FcR on the target cell. The ability of anti-NK1.1 mAb to inhibit direct lysis and enhance redirected lysis is most consistent with NK1.1 being a receptor involved in NK activation.