Acceptance of skin grafts between mice bearing different allelic forms of beta(2)-microglobulin

Single amino acid disparities in MHC class I molecules can elicit transplantation responses. Since beta 2 microglobulin (beta(2)m) is noncovalently associated with class I antigens on the cell membrane we investigated whether the single amino acid polymorphism at position 85 (Asp --> Ala) in the mouse beta(2)m molecule can cause skin graft rejection. A B2m(b) transgene was introduced into CBA(B2m(a)) mice which subsequently expressed both forms of beta(2)m. Skin from these CBA beta(2)m(b) transgenic mice was not rejected by the parental CBA strain. Previous studies showed that cytotoxic T lymphocyte (CTL) responses directed against beta(2)m(b) use H2K(b) as a restriction element. We therefore produced mice expressing H2K(b) and H2A(b) as well as beta 2m(b) by crossing CBA.beta(2)m(b) mice with either CBA.K-b (CBK) transgenic mice or C3H.SW mice and used these as skin graft donors for beta(2)m(b) negative littermates. In both cases rejection of transgenic skin only occurred when mice had received both a beta(2)m(b) graft and an H2-disparate allograft lying adjacent in the same site. Introduction of the male specific antigen, H-Y, as a helper determinant did not result in rejection of beta(2)m(b) skin. Neither did two CTL determinants (P91A and beta(2)m(b)) on the same graft complement one another to elicit a transplantation response. Prior immunisation with tissues expressing the beta(2)m disparity alone did not generate in vivo or in vitro beta(2)m(b)-specific CTL responses, suggesting that this single amino acid difference is not sufficient to elicit a CTL or helper T cell response.