Viral antigen mismatch affects antiviral T-cell response and may impair immunotherapeutic efficacy against adult T-cell leukemia/lymphoma

J Infect Dis. 2024 Sep 20:jiae457. doi: 10.1093/infdis/jiae457. Online ahead of print.

Abstract

HTLV-1 transforms primary CD4+ T cells in vitro within a short time; however, majority of infected individuals maintain an asymptomatic condition, suggesting 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 CTLs. Notably, over half of the 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 ATL by using viral antigen Tax.

Keywords: CD8 T cells; Epitope; HLA-A*2402; HLA-I multimer staining; HTLV-1; Tax-A; Tax-B.