Recognition of naturally processed and ovarian cancer reactive CD8 + T cell epitopes within a promiscuous HLA class II T-helper region of NY-ESO-1

Junko Matsuzaki, Feng Qian, Immanuel Luescher, Shashikant Lele, Gerd Ritter, Protul A. Shrikant, Sacha Gnjatic, Lloyd J. Old, Kunle Odunsi

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

NY-ESO-1 is frequently expressed in epithelial ovarian cancer (EOC) and elicits spontaneous humoral and cellular immune responses in a proportion of EOC patients. The identification of NY-ESO-1 peptide epitopes with dual HLA-class I and class II specificities might be useful in vaccination strategies for generating cognate CD4+ T cell help to augment CD8+ T cell responses. Here, we describe two novel NY-ESO-1-derived MHC class I epitopes from EOC patients with spontaneous humoral immune response to NY-ESO-1. CD8 + T cells derived from NY-ESO-1 seropositive EOC patients were presensitized with a recombinant adenovirus encoding NY-ESO-1or pooled overlapping peptides. These epitopes, ESO127-136 presented by HLA-A68 molecule, and ESO127-135 restricted by HLA-Cw15 allele, are located within ESO119-143, a promiscuous HLA-class II region containing epitopes that bind to multiple HLA-DR alleles. The novel epitopes were naturally processed by APC or naturally presented by tumor cell lines. In addition, these epitopes induced NY-ESO-1-specific CTL in NY-ESO-1 seropositive EOC patients. Together, the results indicate that ESO119-143 epitope has dual HLA classes I and II specificities, and represents a potential vaccine candidate in a large number of cancer patients.

Original languageEnglish (US)
Pages (from-to)1185-1195
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume57
Issue number8
DOIs
StatePublished - Aug 2008

Keywords

  • CD8
  • Epithelial ovarian cancer
  • Epitope
  • MHC class I
  • NY-ESO-1
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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