Genetic control of the immune response to myoglobin. 3. Autoimmune T-lymphocyte proliferative response to mouse myoglobin

Previously, we have reported that antibodies against sperm-whale myoglobin (Mb) raised in several species recognized antigenic sites of sperm-whale Mb that had identical structures to the corresponding regions in the host Mb. Subsequently, autoantibodies were readily generated by immunization with host's autologous Mb. Since the immune responses to spermwhale Mb antigenic sites are under separate genetic control we have examined whether autoantigenic sites are also genetically controlled, and have determined T-cell participation in this autoimmune response. Mouse Mb was isolated from mice of the B10 background and its ability to invoke an autoimmune response in congenic mouse strains, also of the B10 background, was studied. Only the H-2^s haplotype was a high responder. The haplotypes H-2^b, H-2^d, H-2^f, H-2^j, H-2^k, H-2^p, H-2^q, H-2^u and H-2^v were very low or non-responders. Studies with recombinant strains indicated the involvement of two Ir genes in the autoimmune response, one mapping in the I-A (I-B) subregions and the other in the H-2D end.