Cell-mediated cytotoxicity to non-MHC alloantigens on mouse epidermal cells. II. Genetic basis of the response of C3H mice

Epidermal cells (EC) of AKR and CBA (H-2(k)) mouse strains share non-H-2 alloantigens that induce potent cytotoxic T lymphocytes (CTL) in H-2 compatible C3H hosts, and these CTL lyse EC targets in preference to lymphoid cell (LC) targets in H-2-restricted fashion in short-term cell-mediated cytotoxicity (CMC) assays. In contrast, C3H EC are not immunogenic in this regard in AKR and CBA hosts. (C3H x CBA)F₁ hybrid hosts are nonresponders to AKR EC, exactly like the CBA parent strain hosts, and their own EC are immunogenic in C3H hosts and susceptible to lysis by the CTL so generated. Hence, CBA mice express a non-H-2 CMC determinant on EC that is absent on C3H EC. Offspring produced by backcrossing (C3H x CBA)F₁ hybrids to the antigen-negative C3H parent strain were tested individually for their responsiveness to AKR EC immunogens and for the susceptibility of their own EC to lysis by C3H anti-AKR EC effectors. There was a clear 1:1 distribution of the backcross offspring into 2 populations in both test systems. Moreover, responsiveness and antigenicity were inversely correlated in individual mice. Thus, the expression of EC alloantigens in the segregating offspring depends on the activity of genes at a single Mendelian locus. These results are most compatible with the hypothesis that a loss mutation occurred early in the history of the C3H strain at a non-H-2 locus that specifies a system of alloantigens expressed preferentially on EC. The finding that CTL generated by AKR EC immunogens in C3H/Heston and C3H/Andervont mice exhibit the same preferential lysis of EC as opposed to LC targets is consistent with this hypothesis because these C3H strains separated over 40 yr ago. Because this locus does not appear to correspond to any known locus, we have provisionally designated it the Epa (epidermal alloantigen) locus.