EPIDERMAL ALLOANTIGEN AND THE SURVIVAL OF MOUSE SKIN ALLOGRAFTS

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Abstract
Recently, we identified a new non-H-2 alloantigen (epidermal alloantigen (Epa-1)) on mouse epidermal cells (ECs) that evokes potent cytotoxic T cells that lyse ECs preferentially in vitro in H-2-restricted fashion. In the present investigation, we attempted to determine if Epa-1 functions in vivo as a histocompatibility (H) antigen. Epa-1+ skin allografts were rejected consistently, although slightly, faster than Epa-1− grafts in only male hosts in only one of three strain combinations tested. Preimmunization with Epa-1+ ECs was more effective than Epa-1− ECs in evoking second-set skin allograft rejection in hosts of both sexes in the one strain combination tested. However, because of the numerous other non-H-2 alloantigenic differences in the strain combinations used, we could not be sure that the observed differences in test graft survival were attributable to Epa-1. In contrast, with a population of mice produced by back-crossing Epa-1+/Epa-1−F1 hybrids to the Epa 1− strain, matching donors and recipients for Epa-1 only and ignoring all other non-H-2 differences resulted in a very significant incidence of substantially prolonged skin allograft survival. Thus, Epa-1 either is an H antigen itself or is a consistent marker for an as yet undefined H antigen determined by a gene closely linked to the Epa-1 locus. Epa-1 did not function as an Skn-type H antigen to evoke donor-strain allograft rejection and EC-specific alloantibodies in persistent, allogeneic radiation chimeras. However, this is explicable by the fact that Epa-1 is present in immunogenic and, presumably, in tolerogenic form, although not as a target cell determinant, on bone marrow derivatives. Although Epa-1 differences apparently are of little significance when presented in aggregate with numerous other non-H-2 differences, when the latter differences are reduced, as in a backcross population, Epa-1 incompatibility may have a very significant influence on skin allograft survival.
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