Cell-mediated cytotoxicity to non-MHC alloantigens on mouse epidermal cells. III. Epidermal cell-specific cytotoxic T lymphocytes.

We have previously shown that murine epidermal cells (EC) from 5 H-2 compatible donor strains induce cytotoxic T lymphocytes (CTL) in C3H hosts that preferentially lyse donor EC as opposed to donor lymphoid cells (LC). This preference has been shown to be dependent on a single alloantigen disparity, designated epidermal alloantigen (Epa). In this report we studied the specificity of the CTL to determine whether Epa-antigens are in fact EC specific. Two populations of CTL could be identified by cross-immunization, cold-target inhibition, antigen-driven suicide, and limiting-dilution analyses. A minor CTL population recognizes alloantigens that are expressed by both EC and LC, but this population is necessary only for lysis of LC targets. The major CTL population is specific for Epa-antigens and reacts only with EC targets. At the induction phase of CTL responses, donor LC stimulators can weakly stimulate Epa-specific CTL, indicating LC populations express Epa-antigens in immunogenic form but at very low levels compared with EC. The preferential lysis of EC targets in these strain combinations can be attributed to the major Epa-specific CTL population, whereas lysis of LC targets is due to CTL specific for other alloantigens that are shared by EC and LC. The identification of CTL-activating, EC-specific alloantigens may help to explain the extreme immunogenicity of MHC compatible skin allografts.