Immunogenetic control of the response of female mice to male tissue grafts.

Abstract

Inbred strains of mice which carry recombinant H-2 genomes have been utilized to locate the site o f H-2 control of rejection of male liver tissue grafts by females of the same strain. When the K end of the H 2 complex carries the H 2 b allele, the strongest immunological response is evoked in female animals. However, there is a clear participation of the D end of the H 2 complex in immune response to these grafts. The background genome also plays a significant role in graft rejection in some strains. The data presented lead to the hypothesis that control over rejection of these grafts is a complex interaction of multiple genetic factors. The immunological phenomenon of rejection of male skin grafts by female mice of the same inbred strain is well documented (Gasser and Silvers 1972). This reaction is believed to result from immunological reactivity against the H-Y antigen of the male. The H 2 complex, or a gene closely linked to that complex, exerts a major control on the female's ability to reject male skin (Gasser and Silvers 1971, Bailey and Hoste 1971) and capacity to generate cytotoxic killer T lymphocytes against the Y antigen of male cells (von Boehmer et al. 1978). For example, animals carrying the H-2 b haplotype acutely reject male grafts while animals carrying the H 2 a haplotype do not. H 2 b animals are also strong generators of anti-H-Y cytotoxic T lymphocytes. However, attempts to locate the female-vs-male skin-graft response to a specific region of the H-2 complex have produced conflicting results (Bailey 1971). Female B10.A (2R) and B10.A (4R) mice, which are recombinants of the K end of H 2 ~ and the D end of H 2 b, react in the same manner as H-2 a mice while recombinants between the K end of H-2 b and the D end of H-2 a react in a comparable manner to H-2 b females in skin-graft rejection. These data suggest that the response to H-Y is located at or closely linked to the K end of the H-2 complex (Bailey 1971, Stimpfling and Reichert 1971). However, females of the HTG strain give an H-2b-like skin-graft response even though they carry the K region of the H2 d haplotype and the D region of the H 2 b haplotype. It may be concluded from these data that more than one locus is controlling the immune response of the female mice to grafts of male skin. In fact, female mice of the same H-2 type sometimes show significantly different degrees of response to male skin grafts.