Multiple H-2 and non-H-2 genes controlling the antilysozyme response: alternative gene constellations can lead to responsiveness.

Mice carrying the H-2b and H-2s haplotypes are genetically nonresponsive to hen egg-white lysozyme (HEL). Analysis of the anti-HEL response patterns of F1, F2 and backcross progeny showed that responsiveness was dominant and H-2 linked. From plaque-forming cell and serum assays in intra-H-2 recombinant mice, it was established that two I loci were implicated, the possession of either leading to responsiveness to HEL. One of the I genes maps in I-A, and the second in I-C, S or G. While the nonresponse phenotype was determined by the H-2 haplotype, there were codominant non-H-2 genes which contributed to a severe reduction in the level of antibody produced in responder strains. A model is presented attributing the outcome of an encounter with HEL to the regulatory balance of helper and suppressor T cells, which have been activated by different subregions of the major histocompatibility complex.