title: An immunodominant SSX-2-derived epitope recognized by CD4+ T cells in association with HLA-DR.
abstract: Ectopic gene expression in tumors versus normal somatic tissues provides opportunities for the specific immunotargeting of cancer cells. SSX gene products are expressed in tumors of different histological types and can be recognized by tumor-reactive CTLs from cancer patients. Here, we report the identification of an SSX-2-derived immunodominant T cell epitope recognized by CD4(+) T cells from melanoma patients in association with HLA-DR. The epitope maps to the 37-58 region of the protein, encompassing the sequence of the previously defined HLA-A2-restricted immunodominant epitope SSX-2(41-49). SSX-2(37-58)-specific CD4(+) T cells were detected among circulating lymphocytes from the majority of melanoma patients analyzed and among tumor-infiltrating lymphocytes, but not in healthy donors. Together, our data suggest a dominant role of the 37-58 sequence in the induction of cellular CD4(+) T cell responses against SSX antigens and will be instrumental for both the onset and the monitoring of upcoming cancer-vaccine trials using SSX-derived immunogens.
authors.affiliation: Ludwig Institute Clinical Trial Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
authors.forename: Charles S
authors.initials: CS
authors.lastname: Hesdorffer
authors.forename: Monica
authors.initials: M
authors.lastname: Montes
authors.forename: Andrea
authors.initials: A
authors.lastname: Merlo
authors.forename: Daniel
authors.initials: D
authors.lastname: Speiser
authors.forename: Donata
authors.initials: D
authors.lastname: Rimoldi
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Cerottini
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Matthew
authors.initials: M
authors.lastname: Scanlan
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D016056:Immunodominant Epitopes; D008545:Melanoma / Q000276:immunology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D016056:Immunodominant Epitopes; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins