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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 I major histocompatibility antigens. Most of these antigens have been identified in human melanoma, where many of them appear to be tissue-specific, nonmutated proteins expressed by melanoma and normal melanocytes but not by other tissues. There has been much less progress in identifying the tumor antigens on murine tumors that are recognized by T cells, and this has restricted the development of preclinical animal models for immunotherapy. The authors previously described a method for generating tumor-reactive T cells from murine tumors (tumor infiltrating lymphocytes) that are CD8+ T cells recognizing autologous tumor and that can inhibit established tumor on adoptive transfer. Here the authors show that the envelope protein of an endogenous murine retrovirus of the AKV family, found in the germline of the C57BL/6 mouse, is recognized by tumor-infiltrating lymphocytes from two histologically different tumors syngeneic to that mouse strain. Furthermore, the authors identify the specific 9-amino acid peptide from the p15E transmembrane component of this envelope protein that is recognized in the context of major histocompatibility complex Kb, show that it is naturally presented and recognized on several other H-2b tumors, and that cytotoxic T lymphocytes specific for this epitope are therapeutic for these antigen-expressing tumors on adoptive transfer.