GENETIC CONTROL OF THE IMMUNE RESPONSE TO HAEMOGLOBIN:

SUMMARY Mice of independent haplotypes and several recombinant inbred strains were immunized with highly purified preparations of either the α‐chain or β‐chain subunit of human adult haemoglobin. Cells from the sensitized lymph nodes were challenged in vitro with the appropriate subunit (or in some cases both chains) and cell proliferation assessed by 3 H‐thymidine incorporation. Mice of the H‐2 b and H‐2 d haplotypes were high responders to α‐chain while mice of the H‐2 f , H‐2 j , H‐2 k , H‐2 r , H‐2 s , H‐2 u , and H‐2 v haplotypes were low responders. The low responsiveness of B10.A(4R) and B10.MBR and the high responsiveness of B10 indicated that the Ir gene(s) determining responsiveness to the α‐chain subunit resides in the I‐A subregion of the mouse major histocompatibility complex. Mice of the H‐2 d , H‐2 f , and H‐2 s haplotypes were high respoders and H‐2 b , H‐2 f , H‐2 q , and H‐2 u haplotype mice were low responders to β‐chain. H‐2 k , H‐2 p , H‐2 r , and H‐2 v haplotype mice were intermediated responders to β‐chain. The low responsiveness of B10.S(8R) and B10.TL and the high responsivenes of B10.S(9R) mapped the Ir gene(s) to β‐chain to the I‐A subregion. Data collected from challenging high responder cells with both subunits indicated that α‐chain and β‐chain do not crossreact. These results are discussed in reference to earlier observations suggesting that the low responsiveness of some strains of mice to priming and challenging using the intact haemoglobin molecule might be due to a negative regulatory influence mediated by one of the subunits. In the absence of this influence these mice would respond normally.