Genes outside of the mouse major histocompatibility complex (H-2) were found to be capable of specifically reversing the previously described nonresponsiveness to hen egg-white lysozyme (HEL) owing to H-2b immune response (Ir) genes. C3H.SW, BALB.B, and C57L, all of the H-2b haplotype, showed responsiveness to HEL, but not to human lysozyme (H UL). Mapping of the reversing gene(s) was attempted by testing H-2b recombinant inbred (RI) strains of mice carrying C3H, BALB, and C57L non-H-2b genes. Analysis of the strain distribution pattern of responsiveness with both CXB and BXH RI strains was consistent with the location of the responsible site within the H-3 region on chromosome 2. The anti-HEL proliferative responsiveness in two H-3 congenic strains of mice, B10.C(28NX)SN and B10.C-H-3cH-3a, that have BALB/c genes within the H-3 region confirmed the mapping, as well as localized the reversing gene(s) near the Ir-2 gene. The data are discussed with regard to the site of expression of the reversing gene(s) and its mechanism of action.
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