ALLOREACTIVE NATURAL-KILLER-CELLS IN THE RAT - COMPLEX GENETICS OF MAJOR HISTOCOMPATIBILITY COMPLEX CONTROL

A major role for the nonclassical major histocompatibility complex (MH C) class I region, i.e. RT1.C, in controlling rat natural killer (NK) cell alloreactivity has recently been established, and several finding s suggested the existence of NK-triggering alloantigens coded for by t his region. Here,we have extended our studies on the MHC control of NK cell cytotoxicity against concanavalin A-activated T cell blasts by c omparing semi-syngeneic and fully allogeneic combinations, and we show the following: (a) The self MHC exerted a strong influence on the NK allorecognition repertoire. (b) When anti-F-1 hybrid cytolytic activit ies of parental strain NK cells were measured, both recessively and no n-recessively inherited susceptibility patterns emerged. (c) In most c ombinations parental strain cells were lysed by F-1 hybrid NK cells, t hus resembling the hybrid resistance phenomenon described in mice. The cytotoxicity was lower in strain combinations where NK susceptibility was inherited non-recessively, i.e. when parent anti-F-1 reactivity w as detected, than in recessive combinations. (d) LEW.1LM1 (RT1(lm1)) t arget cells, with a deletion in the RT1.C region that includes express ed class I genes, were more sensitive to lysis by MHC matched NK cells (PVG.1L(LEW), RT1(l) than were parental LEW (RT1(l) cells. The effect of the deletion was the opposite when MHC allogeneic (RT1(c), RT1(u)) as well as semi-syngeneic (RT1llC) NK cells were employed, i.e. sensi tivity was decreased. We conclude that certain MHC-encoded antigens, d epending on the haplotype combination of effector and target cells, ma y either trigger or inhibit rat NK cell cytotoxicity. Furthermore, the potential role of peptides bound to MHC class I molecules recognized by NK cells is discussed.