Identification of an SSX-2 Epitope Presented by Dendritic Cells to Circulating Autologous CD4 super(+) T Cells

Accumulating evidence supports the requirement for both tumor-specific CD8 super(+) and CD4 super(+) 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 super(+) T cell responses in cancer patients. In this study we report identification of the first CD4 super(+) T cell epitope encoded by SSX-2. The identified epitope mapped to the 19-34 region of the protein and was recognized by CD4 super(+) 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 super(+) 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 super(+) T cell immunoresponse to tumor Ags occurs in vivo.