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" |