T cell and IR gene regulation of expression of a cross-reactive idiotype.

The immune response to the chemically defined DNP-oligo-L-lysine antigens is under Ir gene control in the guinea pig. Strain 2 (responder) guinea pigs mount a highly specific T cell-mediated and humoral immune response capable of discriminating closely related DNP-peptides. In contrast, strain 13 (nonresponder) animals fail to mount a cell-mediated response, and produce antibody that is only DNP-specific. In these studies a common idiotypic determinant is defined on highly specific anti-epsilon,DNP-Lys10 antibody produced by strain 2 guinea pigs. Ir gene nonresponder antibody is idiotype-negative. The presence of the idiotypic determinant distinguishes responder anti-epsilon,DNP-Lys10 antibody from responder antibodies elicited by structurally related antigens such as epsilon,DNP-Lys9 and alpha,DNP-Lys10-. Investigation of the regulation of idiotype expression demonstrated that production of idiotype-positive antibody requires the presence of viable, antigen-responsive T cells. Moreover, genetic analysis revealed that expression of the shared idiotype correlates directly with the phenotypic expression of I region genes (DTH responsiveness, Ia antigens) in (2 x 13)F1 x 13 backcross and randomly bred Hartley guinea pigs. Thus, Ir gene regulation of the immune response may be reflected in the v region specificities expressed by antigen-specific B cell clones.