Evidence that epidermal alloantigen Epa-1 is an immunogen for murine heart as well as skin allograft rejection.

Epa-1 is a non-H-2 mouse alloantigen defined by MHC-restricted, CD8+ cytotoxic T cells. In vitro it is a strong determinant for the lysis of epidermal cells, fibroblasts, and macrophages but not lymphocytes, and in vivo it functions as a target for skin allograft rejection and cutaneous graft-versus-host reactions. Genetically, Epa-1 appears to be the nonpolymorphic manifestation of a loss mutation. The establishment of C3H.Epa-1 (Epa), an Epa-1+ congenic strain on the Epa-1- C3H/HeJ (C3H) inbred strain background, facilitated the investigation of the role of Epa-1 in skin and heart allograft rejection. C3H females and males rejected first-set Epa skin grafts with median survival times (MSTs) of 20 and 30 days, respectively. However, there was a strong factor of immunization, because all second-set skin allografts were rejected by hosts of both sexes within 10 days. In contrast, all Epa hosts of both sexes permanently accepted C3H skin allografts, consistent with Epa-1 arising from a loss mutation. C3H hosts of both sexes rejected primarily vascularized first-set Epa heart allografts in similar tempo to first-set Epa skin allografts, with MSTs of about 30 days. However, in contrast to the accelerated rejection of skin allografts, sensitized C3H hosts rejected Epa heart allografts in chronic fashion, with some transplants showing very prolonged survival. Thus, Epa-1 is a relatively strong determinant of skin allograft rejection but a weaker determinant of heart allograft rejection.