Identification of an HLA-DR-restricted peptide epitope with a promiscuous binding pattern derived from the cancer testis antigen HOM-MEL-40/SSX2

Int J Cancer. 2004 Nov 20;112(4):661-8. doi: 10.1002/ijc.20461.


The SSX2 gene encodes the tumor-specific antigen HOM-MEL-40/SSX2 expressed in a broad spectrum of tumors of different origin, against which humoral and CD8+ T-cell-mediated MHC-I-restricted responses have been demonstrated. Searching for promiscuous MHC-II-restricted peptides that might be suitable as a CD4+ stimulating vaccine for many patients, we used the SYFPEITHI algorithm and identified a HOM-MEL-40/SSX2-derived pentadecamer epitope (p45-59) that induced specific CD4+ T-cell responses restricted by the HLA-DRB1 subtypes *0701, *1101 and *1302 that have a cumulative prevalence of approximately 25% in the Caucasian population. The CD4+-mediated response against p45-59 and its DR restriction was demonstrated by inhibition with anti-CD4 and HLA-DR antibodies, respectively, and by blocking experiments using HLA-specific antibodies. The natural processing and presentation of p45-59 was demonstrated by recognition of the SSX2+ melanoma cell line Me 275 as well as autologous and allogeneic dendritic cells pulsed with whole-protein SSX2 by T cells with specificity for p45-59. p45-59 was able to induce responses in 3/6 breast cancer patients and 1/5 healthy controls. No correlation was found between CD4+ T-cell responses against p45-59 reactivity and anti-SSX2 antibody titers in the serum of patients, suggesting that CD4+ and B-cell responses are regulated independently. p45-59 holds promise as a broadly applicable peptide vaccine for patients with SSX2-positive neoplasms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Formation
  • Antigens, Neoplasm / immunology*
  • B-Lymphocytes / immunology
  • Breast Neoplasms / genetics*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology*
  • Dendritic Cells
  • Epitopes
  • Female
  • HLA-DR Antigens / genetics*
  • Humans
  • Neoplasm Proteins / genetics*
  • Repressor Proteins / genetics*


  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes
  • HLA-DR Antigens
  • Neoplasm Proteins
  • Repressor Proteins
  • synovial sarcoma X breakpoint proteins