Multiple H‐2 and non‐H‐2 genes controlling the anti‐lysozyme response: Alternative gene constellations can lead to responsiveness

Mice carrying the H‐Z^b and H‐2^s 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.