The objectives of the project are to determine if some of the minor histocompatibility antigens expressed on mouse epidermal cells represent unique, tissue-specific determinants. This will be accomplished by using epidermal cells prepared by trypsinization of adult mouse tail skin as stimulators and targets of lymphocyte-mediated cytotoxicity. The genetic control of the cytotoxicity evoked by antigens expressed by epidermal cells will be characterized. In addition, clones of cytotoxic T lymphocytes generated by immunization with allogeneic epidermal cells will be maintained in continuous culture with the use of T-cell growth factor. The specificity of these monoclonal effector cells will be determined by techniques such as cold-target inhibition and antigen-driven suicide. In addition, their ability to mediate specific skin allograft rejection and skin lesions in graft-versus-host reactions will be determined in vivo by adoptive transfer techniques; the objective here being to determine whether epidermal-specific antigens identified in vitro are responsible for the unusual vulnerability of skin allografts to rejection, on the one hand, and the primary role of the skin as a target tissue in graft-versus-host-disease.