GENETIC CONTROL OF THE IMMUNE RESPONSE In Vitro Stimulation of Lymphocytes by (T,G)-A--L, (H,G)-A--L, and (Phe, G)-A--L*

Ir-IA is a dominant autosomal gene(s) which regulates the specific antibody response to several antigens, including three branched, multichain, polypeptide antigens, poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys; poly-L-(His, Glu)-poly-D,L-Ala--poly-L-Lys; and polyL-(Phe,Glu)-poly-D,a-Ala--poly-L-Lys, abbreviated respectively (T,G)-A--L, (H,G)-A--L, and (Phe, G)-A--L (1). 1 The Ir-lA gene is located within the H-2 region of the mouse, between the K end and another immune response gene, Ir-lB, which in turn maps between Ir-lA and the Ss-Slp genes, in the middle of the H-2 region (2-4). Adoptive transfer experiments have demonstrated that the IrlA gene is expressed in lymphoid cells. Ir-lA-regulated immune responsiveness was found to be transferable with lymphocytes from high responder animals transferred into lethally irradiated low responder animals (5). The genetic defect in the low responders appears to be expressed in thymus-derived (T) cells, as demonstrated by the following experiments: (a) low responder animals give a normal immune response when immunized with (T,G)-A--L coupled to a highly immunogenic carrier such as methylated bovine serum albumin (6, 7); (b) the primary IgM response elicited by aqueous immunization is equal in high and low responder animals, and this primary response is not dependent on the presence of T cells, since irradiated, thymectomized, bone marrow reconstituted, high and low responder animals are capable of a normal IgM response to (T,G)-A--L while only the intact responder animals make an IgG secondary response (8, 9); (c) tetraparental mice prepared from high and low responder embryos produce high amounts of antibody of the low responder allotype (10). In contrast to these results, limiting dilution experiments of Shearer et al. have suggested that the genetic defect in the response to (Phe,G)-A--L is expressed in both T and B cells (11) and that the genetic defect in the response to (T,G)-A--L is expressed only in B cells (12). The former data, and the antigen-specific nature of the regulation, suggest that the IrlA gene-product is expressed on T