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A Large Number of T Lymphocytes Recognize Moloney-Murine Leukemia Virus-Induced Antigens, but a Few Mediate Long-Lasting Tumor Immunosurveillance ¹

Antonella Facchinetti^*, Silvia Dalla Santa^*, Silvio Mezzalira^*, Antonio Rosato^* and Giovanni Biasi^2,

^* Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy; and Department of Molecular Pathology and Experimental Therapies, Polytechnic University of the Marche, Ancona, Italy

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 chain rearrangements. In mice lacking T cells expressing these TCRV, we demonstrate that alternative TCRV can substitute for the lack of the dominant TCRV 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 rescues the alternative V response. The mechanism of clonal T cell "immunodomination" that guides the preferential V expansion is likely the result of a proliferative advantage of T cells expressing dominant V, 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 gene rearrangements. The ability of T cells expressing alternative TCRV rearrangements to mediate tumor protection was evaluated by a challenge with M-MuLV tumor cells. Although T cells expressing alternative V 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.

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