Effect of Viral Antigen Mismatch on Antiviral T-Cell Response and Immunotherapeutic Efficacy Against Adult T-Cell Leukemia/Lymphoma

Human T-cell leukemia virus type 1 (HTLV-1) transforms primary CD4 T cells in vitro within a short time; however, majority of infected individuals maintain an asymptomatic condition, suggesting that there is an equilibrium between the infected cells and the host immunity. In this study, we identified a variation in a major viral antigen epitope, HTLV-1 Tax301-309, in HLA-A24-positive individuals. Mismatch in A24/Tax301-309 multimers impaired detection of anti-Tax cytotoxic T lymphocytes (CTLs). Notably, more than half of the T-cell receptors (TCRs) of the anti-Tax CTLs did not recognize mismatched Tax301-309 peptides. These findings highlighted the importance of matching the viral antigen epitope type in T-cell-based immunotherapy against adult T-cell leukemia/lymphoma by using viral antigen Tax.