Identification of an SSX-2 epitope presented by dendritic cells to circulating autologous CD4+ T cells Journal Article


Authors: Ayyoub, M.; Hesdorffer, C. S.; Metthez, G.; Stevaovic, S.; Ritter, G.; Che, Y. T.; Old, L. J.; Speiser, D.; Cerottii, J. C.; Valmori, D.
Article Title: Identification of an SSX-2 epitope presented by dendritic cells to circulating autologous CD4+ T cells
Abstract: 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-DPBI*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.
Keywords: controlled study; human cell; t lymphocyte; gene; melanoma; dendritic cell; neoplasm proteins; alleles; tumor antigen; antigen presentation; dendritic cells; amino acid sequence; molecular sequence data; cell culture; immunogenicity; major histocompatibility antigen class 2; antigen recognition; cd4-positive t-lymphocytes; epitope mapping; peptide fragments; epitope; cd4 antigen; epitopes, t-lymphocyte; repressor proteins; antigen-presenting cells; major histocompatibility complex restriction; tissue culture; tumor immunology; hla dp antigen; ssx 2 gene; humans; human; priority journal; article; synovial sarcoma x breakpoint 2 gene; hla-dp antigens
Journal Title: Journal of Immunology
Volume: 172
Issue: 11
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2004-06-01
Start Page: 7206
End Page: 7211
Language: English
PROVIDER: scopus
PUBMED: 15153546
DOI: 10.4049/​jimmunol.172.11.7206
DOI/URL:
Notes: J. Immunol. -- Cited By (since 1996):13 -- Export Date: 16 June 2014 -- CODEN: JOIMA C2 - 15153546 -- Source: Scopus
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  1. Gerd Ritter
    166 Ritter
  2. Lloyd J Old
    593 Old