Genetic control of the immune response to myoglobins. VI. Distinct <i>Ir</i> genes for different myoglobins: complementing genes in <i>I-A</i> and <i>H-2D</i> for equine myoglobin.

Abstract

Abstract The genetic control of the antibody response to equine myoglobin was found to be completely different from that for sperm whale myoglobin, even though they share 87% of their primary sequence and nearly identical three-dimensional structures. Not only were the high- and low-responder haplotypes different for the two myoglobins, but the Ir genes mapped in different subrogions of H-2. The response to sperm whale myoglobin was controlled by two genes in I-A and I-C regulating responses to different subsets of determinants, whereas the response to equine myoglobin was controlled by complementing Ir genes in I-A and H-2D. The latter mapping is based on two independent pairs of strains (B10.A vs B10.A(2R) and B10.BR vs B10.AKM), each of which differ only at H-2D (and possibly, closely linked loci not yet defined) and was confirmed using a strain bearing the H-2dm1 mutation in the H-2D/L region. Most / region Ir genes have been found to be associated with genetic restriction elements involved in antigen presentation. Because H-2D has not previously been implicated in presentation of soluble antigens for antibody responses, either antigen presentation of equine myoglobin is unusual, or the Ir gene mapping in H-2D acts by a different mechanism from those in the I region, or a new class II (la-like) antigen maps extremely close to H-2D. Although the Ir genes were distinct, virtually all the antibodies raised to equine myoglobin cross-reacted with sperm whale myoglobin, albeit with lower affinity, even in strains which were low responders to sperm whale myoglobin.