Analysis of H-2 mutants: Evidence for multiple CML target specificities controlled by the H-2K^b gene

C57BL/6 (H-2^b) mice and two mutants derived from this strain, B6.C-H-2^ba (Hz1) and E6-H-2^bd (M505), were studied in a number of functional tests, in vitro and in vivo, that assay for differences at the H-2 complex. All three strains give rise to reciprocal mixed lymphocyte reactivity (MLR) and cell-mediated lympholysis (CML) in vitro as well as graft-host reactivity (GVHR) and skin graft rejection in vivo. Analysis for cross-reactivity between these strains in CML revealed that the gained antigens in each mutant do not cross-react, and that Hz1 has lost an antigen shared by C57BL/6 and M505 strains. In addition, spleen cells from B10.A(4R) mice, which differ from the H-2^b haplotype only at the K end of the H-2 complex, recognize a common antigen shared by all three strains tested. Provided that the mutations occurred in the H-2K^b gene, these data indicate that a) there are at least three antigenic specificities coded for by the H-2K^b gene(s) that serve as targets for receptors on thymus-derived (T) cells in CML; b) since C57BL/6 strain mice and the mutants are serologically indistinguishable on a qualitative basis, the antigens recognized by the receptors on T cells and by humoral H-2 antibody are nonidentical; and c) mutation in the H-2K^b locus itself can give rise to allogeneic recognition phenomena such as MLR and GVHR.