GENETIC CONTROL OF THE IMMUNE RESPONSE TO HAEMOGLOBIN:

Abstract

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 Hb. 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 haplotypes were low responders. The low responsiveness of B10.A(4R) and B10.MBR and the high responsiveness of B10 indicated that the Ir [immune response] 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-2q 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 responsiveness 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 subunits indicated that .alpha.-chain and .beta.-chain do not crossreact. The low responsiveness of some strains of mice to priming and challenging using the intact Hb molecule might be due to a negative regulatory influence mediated by 1 of the subunits. In the absence of this influence these mice would respond normally.