Accumulating evidence supports the requirement for both
tumor-specific CD8(+) and CD4(+) T cell responses for efficient
tumor rejection to occur. Because of its expression in different
tumor types, the
cancer/testis Ag encoded by the
synovial sarcoma X breakpoint 2 (SSX-2) gene is among the most relevant candidates for the development of generic
cancer vaccines. The immunogenicity of SSX-2 has been previously corroborated by detection of specific humoral and CD8(+) T cell responses in
cancer patients. In this study we report identification of the first CD4(+)
T cell epitope encoded by SSX-2. The identified
epitope mapped to the 19-34 region of the
protein and was recognized by CD4(+) T cells from an Ag-expressing
melanoma patient in association with
HLA-DPB1*0101. The absence of detectable response in healthy donors and other patients suggests that SSX-2-specific CD4(+) T cells in the responder patient had been previously expanded in vivo in response to the autologous
tumor. The
epitope did not appear to be presented on the surface of
tumor cells at levels sufficient to allow direct recognition. In contrast, it was efficiently presented by autologous dendritic cells, supporting the concept that processing by professional APC is the main pathway through which the CD4(+) T cell immunoresponse to
tumor Ags occurs in vivo.