Genetic control of the immune response to haemoglobin. II. Studies using purified alpha-chain and beta-chain as immunogens.

Mice of independent haplotypes and several recombinant inbred strains were immunized with highly purified preparations of either the alpha-chain or beta-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 3H-thymidine incorporation. Mice of the H-2b and H-2d haplotypes were high responders to alpha-chain while mice of the H-2f, H-2j, H-2k, H-2r, H-2s, H-2u, and H-2v haplotype were low responders. the low responsivenesss of B10.A(4R) and B 10.MBR and high responsiveness of B10 indicated that the Ir gene(s) determining responsiveness to the alpha-chain subunit resides in the I-A subregion of the mouse major histocompatibility complex. Mice of the H-2d, H-2f, and H-2s haplotypes were high responders and H-2b, H-2j, H-2a, and H-2u haplotype mice were low responders to beta-chain. H-2k, H-2p, H-2r, and H-2v haplotype mice were intermediate responders to beta-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 beta-chain to the I-A subregion. Data collected from challenging high responder cells with both subunit indicated that alpha-chain and beta-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.