The envelope protein of an endogenous murine retrovirus is a tumor-associated T-cell antigen for multiple murine tumors

Recently, significant progress has been made in identifying specific tumor- associated antigens recognized by T cells and defining the specific peptide epitopes within these proteins that are processed and presented on class 1 major histocompatibility antigens. Most of these antigens have been identi fied in human melanoma, where many of them appear to be tissue-specific, no nmutated proteins expressed by melanoma and normal melanocytes but not by o ther tissues. There has been much less progress in identifying the tumor an tigens on murine tumors that are recognized by T cells, and this has restri cted the development of preclinical animal models for immunotherapy. The au thors previously described a method for generating tumor-reactive T cells f rom murine tumors (tumor infiltrating lymphocytes) that are CD8(+) T cells recognizing autologous tumor and that can inhibit established tumor on adop tive transfer. Here the authors show that the envelope protein of an endoge nous murine retrovirus of the AKV family, found in the germline of the C57B L/6 mouse, is recognized by tumor-infiltrating lymphocytes from two histolo gically different tumors syngeneic to that mouse strain. Furthermore, the a uthors identify the specific 9-amino acid peptide from the p15E transmembra ne component of this envelope protein that is recognized in the context of major histocompatibility complex Kb, show that it is naturally presented an d recognized on several other H-2(b) tumors, and that cytotoxic T lymphocyt es specific for this epitope are therapeutic for these antigen-expressing t umors on adoptive transfer.