Gain/loss of poly(Glu50Tyr50)/poly(Glu60Ala30Tyr10) responsiveness in the bm12 mutant strain.

The development of inbred strains of mutant mice has proven useful in ascribing specific gene functions to particular genetic loci within the regions and subregions of the H-2 complex. The B6.C-H-2bm12 (bm12) strain is of particular interest in that, compared to parental C57Bl/6Kh (B6) mice, it bears a presumptive single gene mutation altering the Ab beta chain encoded by the I-A subregion. Our data show that bm12 mice have gained the ability to respond to poly(Glu50Tyr50)(GT) and have lost the ability to make plaque-forming cell or delayed-type hypersensitivity responses to the closely related copolymer, poly(Glu60Ala30Tyr10)(GAT), although retaining the ability to mount a GAT-specific T cell proliferative response. This is in sharp contrast to the parental B6 strain, which is a GT nonresponder and a GAT responder. Thus, this study is the first to report the establishment of responder status as a consequence of mutation. Possible mechanisms accounting for the gain/loss of GT/GAT responsiveness in the context of a two-step helper T cell model are discussed.