Identification of an SSX-2 epitope presented by dendritic cells to circulating autologous CD4+ T cells.
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.
Ayyoub
Maha
M
Ludwig Institute Clinical Trial Center and Division of Medical Oncology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Hesdorffer
Charles S
CS
Metthez
Genevieve
G
Stevanovic
Stefan
S
Ritter
Gerd
G
Chen
Yao-Tseng
YT
Old
Lloyd J
LJ
Speiser
Daniel
D
Cerottini
Jean-Charles
JC
Valmori
Danila
D
D000483:Alleles; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000276:immunology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins