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 Journal Article


Authors: Matsuzaki, J.; Qian, F.; Luescher, I.; Lele, S.; Ritter, G.; Shrikant, P. A.; Gnjatic, S.; Old, L. J.; Odunsi, K.
Article Title: 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
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. © 2008 Springer-Verlag.
Keywords: controlled study; human tissue; human cell; flow cytometry; sensitivity and specificity; cd8+ t lymphocyte; cd8-positive t-lymphocytes; ovarian neoplasms; allele; ovary cancer; cell line, tumor; antigen presentation; tumor necrosis factor alpha; gamma interferon; drug mechanism; molecular recognition; ny eso 1 antigen; hla antigen class 2; epitope; cytotoxic t lymphocyte; tumor cell line; hla antigen class 1; histocompatibility antigens class i; tumor immunity; cytokine production; t-lymphocytes, helper-inducer; virus recombinant; histocompatibility antigens class ii; epithelial ovarian cancer; epitopes, t-lymphocyte; humoral immunity; antigen presenting cell; major histocompatibility antigen class 1; hla system; peptide derivative; ny-eso-1; adenovirus; cd8; t lymphocyte antigen; mhc class i; hla a68 antigen; hla cw15 antigen; prolylglycylvalylleucylleucyllysylglutamylphenylalanyl threonylvalylserylglycylasparaginylisoleucylleucylthreonylisoleucylarginyl leucylthreonylalanylalanylaspartylhistidylarginine; threonylvalylserylglycylasparaginylisoleucylleucylthreonylisoleucine; valylserylglycylasparaginylisoleucylleucylthreonylisoleucylarginine
Journal Title: Cancer Immunology, Immunotherapy
Volume: 57
Issue: 8
ISSN: 0340-7004
Publisher: Springer  
Date Published: 2008-08-01
Start Page: 1185
End Page: 1195
Language: English
DOI: 10.1007/s00262-008-0450-4
PUBMED: 18253733
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 9" - "Export Date: 17 November 2011" - "CODEN: CIIMD" - "Source: Scopus"
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MSK Authors
  1. Sacha Gnjatic
    113 Gnjatic
  2. Gerd Ritter
    166 Ritter
  3. Lloyd J Old
    593 Old