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 design

Abstract

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.

Fig. 1

A, the NY-ESO-1 tumor antigen contained overlapping CTL and HTC epitopes. The smaller box indicates the HLA-A2-restricted CTL epitope and the larger box indicates the core region of the HLA-DP4-restricted HTC epitope (9). Peptides used in this study are also listed. B, peptides of various lengths recognized by CD4+ CT4–1 clone 12C. C, peptides of various lengths recognized by CD8+ TE8–1 clone 8F. D, ESO:157–170 peptide pulsed on 1088 EBV B cells (A2+, DP4+) at different concentrations were recognized by both CD4+ and CD8+ T cell clones. E, activities of selected cell cultures after CD4+ or CD8+ T-cell purification. T-cell cultures as listed in Table 1 were purified using a negative selection beads (“Materials and Methods”), then incubated with the indicated targets. Explanation of legend: e.g., BL157–167, cultures from patient BL generated with ESO:157–167 peptide.