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 2 mutants derived from this strain, B6 C H2(ba) (Hz1) and B6 H2(bd) (M505), were studied in a number of functional tests, in vitro and in vivo, that assay for differences at the H2 complex. All 3 strains give rise to reciprocal mixed lymphocyte reactivity (MLR) and cell mediated lympholysis (CML) in vitro, as well as graft versus 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 H2(b) haplotype only at the K end of the H2 complex, recognize a common antigen shared by all 3 strains tested. Provided that the mutations occurred in the H2 K(b) gene, these data indicate that there are at least 3 antigenic specificities coded for by the H2 K(b) gene(s) that serve as targets for receptors on thymus derived (T) cells in CML. 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 H2 antibody are nonidentical; and mutation in the H2 K(b) locus itself can give rise to allogeneic recognition phenomena such as MLR and GVHR.