V. influence of the ga and gt immune response genes on the specificity of cellular and humoral immune responses to a terpolymer of l-glutamic

Histocompatibility-linked specific immune response (Jr) I genes, controlling the ability to develop cellular and humoral immune responses, have been identified in guinea pigs and mice (1). Two experimental approaches used to identify Ir genes and to investigate their function have been the study of immunogenicity of synthetic polypeptides of limited structural diversity, and the study of the immunogenicity of native protein antigens injected in limiting immunizing doses. In earlier reports we have identified four Ir genes in inbred and random-bred guinea pigs, the "PLL, . . . . GA, . . . . GT," and "L-BSA" genes controlling, respectively, immune responsiveness to hapten-poly-L-lysine conjugates, to random eopolymers of L-glutamic acid and L-alanine (GA), and to L-glutamic acid and L-tyrosine (GT), and to limiting immunizing doses of bovine serum albumin (BSA) (2-4). Inbred strain 2 guinea pigs are homozygous for the PLL, GA, and L-BSA genes which were shown to be very closely linked to the major locus controlling strain 2 histocompatibility antigens (4-7). The GT gene is found in strain 13 guinea pigs and is similarly linked to a major strain 13 histocompatibility specificity (7). Furthermore, in most random-bred guinea pigs the GA and PLL genes remain linked and behave as alleles or pseudoalleles to the GT gene (8). The successful transfer of immune responsiveness controlled by the PLL gene to