Many studies have demonstrated that the mammalian host can mount a variety of immune responses to invading tumor cells. One such response involves the production of cytotoxic T cells (CTL) that kill tumor cells. Major histocompatability complex (MHC) antigens are critical targets on tumor cells for CTL recognition. Therefore, an understanding of the regulation of MHC antigens on tumor ceIls would further our understanding of tumor rejection. These studies will enhance our knowledge of MHC antigen expression on murine 402AX teratocarcinoma cells. Previous studies from this laboratory have established that: (1) resistance to this tumor is under the genetic control of two genes; (2) resistant animals have the ability to induce MHC antigen expression on the normally MHC-negative 402AX cells; and (3) host-induced, tumor cell MHC antigen expression is regulated by splenic T cells. The current studies will determine: (1) the population of host lymphoid cells that regulate MHC antigen on 402AX cells in vivo; (2) the genetic control of MHC antigen induction of 402AX; (3) the biochemical characterization of 402AX MHC antigens; (4) the role of beta-2-microglobulin in MHC antigen expression on 402AX; (5) the cellular mechanism(s) of tumor cell MHC expression; (6) the precise MHC antigens expressed on 402AX; (7) the molecular level of regulation of MHC antigens on 402AX; (8) the relationship of MHC antigen expression to 402AX cellular differentiation; (9) the stage of the host's immune response to the tumor during which MHC antigens are important; and (10) the tumor-specific transplantation antigens recognized in conjunction with tumor cell MHC antigens. The results of these experiments will increase our knowledge of MHC antigen regulation on tumor cells and may improve our ability to manipulate a host's immune response against a tumor. (AG)