LACK OF F1 ANTIPARENTAL RESISTANCE IN H-2(B D) F1 HYBRIDS DEVOID OF BETA(2)-MICROGLOBULIN/

F-1 hybrid mice often reject parental hematopoietic grafts, a phenomen on known as hybrid resistance. Hybrid resistance is mediated by natura l killer (NK) cells and although the molecular interactions responsibl e for this phenomenon are largely unknown, one hypothesis suggests tha t parental cells are rejected because they fail to express a complete set of host major histocompatibility complex (MHC) class I molecules. Inherent in this theory is that NK cells in the F-1 hybrid are instruc ted by self MHC class I molecules to form an NK cell repertoire capabl e of reacting against cells lacking these self MHC class I molecules. Here, we show that C57BL/6 x DBA/2 mice (H-2(b/d)) devoid of beta(2)-m icroglobulin (beta(2)m) are incapable of rejecting beta(2)m-/- parenta l C57BL/6 cells (H-2(b)) both in vivo and in vitro. From this, we conc lude that the development of an NK cell repertoire, at least in F-1 mi ce of the H-2(b/d) haplotype, requires expression of MHC class I molec ules complexed with beta(2)m.