In vitro peptide immunization of target tax protein human T-cell leukemia virus type 1-specific CD4+ helper T lymphocytes.

PURPOSE: Adult T-cell leukemia/lymphoma induced by human T-cell leukemia virus type 1 (HTLV-1) is usually a fatal lymphoproliferative malignant disease. HTLV-1 Tax protein plays a critical role in HTLV-1-associated leukemogenesis and is an attractive target for vaccine development. Although HTLV-1 Tax is the most dominant antigen for HTLV-1-specific CD8(+) CTLs in HTLV-1-infected individuals, few epitopes recognized by CD4(+) helper T lymphocytes in HTLV-1 Tax protein have been described. The aim of the present study was to study T-helper-cell responses to HTLV-1 Tax and to identify naturally processed MHC class II-restricted epitopes that could be used for vaccine development. EXPERIMENTAL DESIGN: An MHC class II binding peptide algorithm was used to predict potential T-helper cell epitope peptides from HTLV-1 Tax. We assessed the ability of the corresponding peptides to elicit helper T-cell responses by in vitro vaccination of purified CD4(+) T lymphocytes. RESULTS: Peptides Tax(191-205) and Tax(305-319) were effective in inducing T-helper-cell responses. Although Tax(191-205) was restricted by the HLA-DR1 and DR9 alleles, responses to Tax(305-319) were restricted by either DR15 or DQ9. Both these epitopes were found to be naturally processed by HTLV-1(+) T-cell lymphoma cells and by autologous antigen-presenting cells that were pulsed with HTLV-1 Tax(+) tumor lysates. Notably, the two newly identified helper T-cell epitopes are found to lie proximal to known CTL epitopes, which will facilitate the development of prophylactic peptide-based vaccine capable of inducing simultaneous CTL and T-helper responses. CONCLUSION: Our data suggest that HTLV-1 Tax protein could serve as tumor-associated antigen for CD4(+) helper T cells and that the present epitopes might be used for T-cell-based immunotherapy against tumors expressing HTLV-1.