Murine responses to both the male specific histocompatibility antigen H-Y and the erythrocyte alloantigen Ea-1 are regulated by genetic factors. In each case a single major gene that controls the immune response has been identified, but additional modifying factors can be demonstrated if appropriate strain combinations are studied. A single gene controlling the response to Ea-1 antigens, which segregates when strains YBR and B10.D2 are crossed, has been shown not to be an allele of the Ir-2 locus. A new phenomenon has also been observed in the control of anti-Ea-1 antibody production in that the mating of two responding strains, YBR and HTG, produces an F 1 generation of complete nonresponders. By linkage tests it was shown that the responding strain HTG possesses the nonresponder allele at the Ir- 2 locus, so there appear to be recessive genes in the background which are able to overcome the suppressive influence of this allele
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