Idiotypic analysis of lymphocytes in vitro. II. Genetic control of T-helper cell responsiveness to anti-idiotypic antibody.

When the IgG1 fraction of anti-idiotypic antibodies raised in guinea pigs is injected into mice, sensitization of idiotypic T and B lymphocytes occurs (1-3). In the present study we analyze the genetic requirements for T-helper cell sensitization by anti-idiotypic antibody. This was done by measuring, in a suitable panel of mouse strains, helper cell responsiveness to two anti-idiotypic reagents which recognize distinct, strain-specific idiotypes, namely the A5A and the S117 marker. Whenever helper cell sensitization by anti-idiotypic antibody was successful, helper function could be specifically inhibited by the same and only the same anti-idiotype. This indicates that helper cells induced by anti-idiotypic antibody express idiotypic determinants on their receptors for antigen. Helper cell sensitization by anti-idiotypic antibody was found in all strains expressing the corresponding or a cross-reactive idiotype at the immunoglobulin level. Idiotype-negative strains were always unresponsive to anti-idiotypic stimulation. In addition, responsiveness did not depend on the H-2 haplotype. Since the A5A and the S117 idiotype are markers for V genes in the heavy-chain linkage group, the present results support the view that the same genes in the Ig-1 complex code for variable portions of immunoglobulins and T-helper cell receptors.