GENETIC CONTROL OF THE IMMUNE RESPONSE TO HAEMOGLOBIN: I. DEMONSTRATION OF SEPARATE GENETIC CONTROL OF THE RESPONSES TO THE α‐ AND β‐SUBUNITS BY IN VITRO LYMPHOCYTE PROLIFERATION

These studies were undertaken to analyse the genetic control of the immune response to an oligomeric protein and the role of individual subunits in the regulation of the response. Human adult haemoglobin (Hb) was selected as a model for these studies because it is a well‐characterized protein and its antigenic structure is being determined in our laboratories. Mice of various congenic strains were immunized with Hb and the lymph node cells from Hb‐primed mice were challenged in vitro with Hb, and its α‐chain and β‐chains as well as an appropriate control antigen. Lymphocyte proliferation was determined by ³H‐thymidine incorporation. The data collected indicated that mice of the H‐2^b and H‐2^d haplotypes were high responders while H‐2^k, H‐2^s, H‐2^q and H‐2^j haplotype mice were low responders to Hb. Studies with H‐2 recombinant strains indicated that the immune response to Hb and its subunits is determined by genes in the I‐A subregion and the D end of the H‐2 complex. The significance of these findings in terms of control and regulation of the overall response to native Hb are discussed.