A large number of T lymphocytes recognize Moloney-murine leukemia virus-induced antigens, but a few mediate long-lasting tumor immunosurveillance

The CD8(+) T cell response to Moloney-murine leukemia virus (M-MuLV)-induced Ags is almost entirely dominated by the exclusive expansion of lymphocytes that use preferential TCRV beta chain rearrangements. In mice lacking T cells expressing these TCRV beta, we demonstrate that alternative TCRV beta can substitute for the lack of the dominant TCRV beta in the H-2-restricted M-MuLV Ag recognition. We show that, at least for the H-2(b)-restricted response, the shift of TCR usage is not related to a variation of the immunodominant M-MuLV epitope recognition. After virus immunization, all the potentially M-MuLV-reactive lymphocytes are primed, but only the deletion of dominant V beta rescues the alternative V beta response. The mechanism of clonal T cell "immunodomination" that guides the preferential V beta expansion is likely the result of a proliferative advantage of T cells expressing dominant V beta, due to differences in TCR affinity and/or cosignal requirements. In this regard, a CD8 involvement is strictly required for the virus-specific cytotoxic activity of CTL expressing alternative, but not dominant, V beta gene rearrangements. The ability of T cells expressing alternative TCRV beta rearrangements to mediate tumor protection was evaluated by a challenge with M-MuLV tumor cells. Although T cells expressing alternative V beta chains were activated and expanded, they were not able to control tumor growth in a long-lasting manner due to their incapacity of conversion and accumulation in the T central memory pool.