Genetic control of the immune response to collagen. I. Quantitative determination of response levels by multiple I-region genes.

The antibody response in mice to type I calf skin collagen is quantitatively determined by genes with map to the I region of the H-2 histocompatibility complex. The use of H-2 recombinant B10 congenic strains of mice reveals that a gene in the IA subregion and a gene to the right of the IA subregion affect responsiveness. To examine complementation patterns in the antibody response to collagen, five B10 congenic strains, each bearing an independent H-2 haplotype, were intercrossed to obtain nine hybrid strains heterozygous at the H-2 locus. In five combinations heterozygous progeny produced significantly greater antibody responses than those observed for the homozygous parental strains. Two low responder haplotypes, H-2k and H-2d, were shown to be qualitatively different. Mice of these haplotypes show a different dose--response pattern and a different phenotypic pattern of inheritance with respect to the high responder H-2b haplotype. Complementation effects found in F1 hybrid mice derived from H-2 recombinant parental strains indicate that high responsiveness, controlled by an IA6 subregion gene, can be influenced by an interaction between an IAk subregion gene and an ICd subregion gene on different chromosomes. These data are consistent with the possibility that there exist two or more I region genes that have distinct functions and can interact to affect the levels of immune responsiveness.