Gain/loss of Poly(glun°tyr~°)/ Poly(glu6°ala3°tyri°) Responsiveness in the Bml2 Mutant Strain*

Specific immune responses to thymus-dependent antigens involve multiple stages of cell interaction. Initiation of an immune response requires the presentation of antigen by macrophages, as well as the successful interaction of multiple subsets of T cells. In the mouse, both antigen recognition and the production of antigen-specific T cell factors by helper (Th) 1 or suppressor (Ts) T cells appear to be controlled b y / region genes of the major histocompatibility complex (H-2) (1, 2). Immune responseassociated (Ia) molecules found on most B cells, and to varying degrees on macrophages and T cells, are encoded by genes in the I-A and I-E subregions and may well be products of immune response (Ir) and/or immune suppressor (Is) genes (3-5). Successful T-B cell collaboration requires identity of genes, or their products, in the I-A subregion (3). The development of inbred strains of mutant mice has proven useful in ascribing specific gene fractions to particular genetic loci within the regions and subregions of the H-2 complex (6). The B6.C-H-2 b'~l~ (bml2) strain is of particular interest in that it bears a presumptive single gene mutation altering the A~ chain, encoded in the I-A subregion, and is characterized by changes in serologically defined Ia determinants, by strong graft rejection, and by mixed lymphocyte response between parent and mutant (7-14). Mice of the bml2 strain have impaired immune responses, relative to the parental strain C57BI/6Kh (B6), to beef insulin (15), to H-Y antigen (11), and to the alpha chain of human hemoglobin (16). In contrast, bml2 immune responses to other antigens, such as poly(L-Tyr,L-Glu)-poly(DL-Ala)--poly(L-Lys) [(T,G)-A--L], poly(L-Phe,L-Glu)-poly(DL-Ala)--poly(L-Lys) [(Phe,G)-A--L], and poly(L-His,L-Glu)poly(DL-Ala)--poly(L-Lys) [(H,G)-A--L], do not differ markedly from parental B6 mice (11, 15, 17). Although the immune responsiveness to beef insulin, H-Y antigen, human