Immunogenetic analysis of H-2 mutations. II. Cellular immunity to the H-2(da) mutation

The H-2(da) haplotype was derived from the H-2(d) haplotype by a mutation localized to the D end of the H-2 complex. Coculture of H-2(d) and H-2(da) spleen cells gives rise to bidirectional MLR. However, the H-2(d) anti H-2(da) response is much stronger than that of H-2(da) anti H-2(d). Both haplotypes give rise to reciprocal CML. B10.D2(R103) strain spleen cells, which differ only at the D end of the H-2 complex from the H-2(d) haplotype, kill H-2(da) target cells in CML when sensitized to H-2(d) stimulators and vice versa. Therefore, both the mutant and strain of origin share a D end CML specificity. H-2(d) and H-2(da) reject skin grafts in both directions, although some H-2(d) grafts show prolonged acceptance on H-2(da) recipients. These data are consistent with a mutation in the D end of the H-2(d) haplotype resulting in gain loss of an antigen(s) that gives rise to reciprocal MLR, CML, and skin graft rejection. Further, the mutant can be distinguished from the strain of origin on the basis of the strength of immune response in MLR.