Generation of NY-ESO-1-specific CD4 and CD8 T Cells by a Single Peptide with Dual MHC Class I and Class II Specificities: A New Strategy for Vaccine

Gang Zeng,1 Yong Li, Mona El-Gamil, John Sidney, Alexandro Sette, Rong-fu Wang, Steven A. Rosenberg, and Paul F. Robbins

The existence of overlapping CD8+ and CD4+  T-cell epitopes within certain tumor antigens provides an opportunity to test the hypothesis that relatively short peptides could be used to generate both CD8+ and CD4+  T cells against tumor. In this report, T-cell responses to a fragment of the tumor antigen NY-ESO-1 that contained an HLA-DP4-restricted helper T cell epitope as well as an HLA-A2-restricted cytotoxic T cell epitope were analyzed. One peptide, ESO:157–170 (SLLMWITQCFLPVF) was recognized by both NY-ESO-1-reactive CD8  and CD4 T-cell clones. Both CD4+ and CD8+ T cells were efficiently generated from the peripheral blood of multiple melanoma patients after in vitro stimulations using ESO:157–170. Dual-specific peptides containing both cytotoxic T-cell and helper T-cell epitopes may represent an attractive strategy of vaccine design aimed at generating tumor-reactive CD4+ and CD8+ T cells.