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One NY-ESO-1-derived epitope that promiscuously binds to multiple HLA-DR and HLA-DP4 molecules and stimulates autologous CD4+ T cells from patients with NY-ESO-1-expressing melanoma.

Abstract
NY-ESO-1 is expressed by a broad range of human tumors and is often recognized by Abs in the sera of cancer patients with NY-ESO-1-expressing tumors. The NY-ESO-1 gene also encodes several MHC class I- and class II-restricted tumor epitopes recognized by T lymphocytes. In this study we report one novel pan-MHC class II-restricted peptide sequence, NY-ESO-1 87-111, that is capable of binding to multiple HLA-DR and HLA-DP4 molecules, including HLA-DRB1*0101, 0401, 0701, and 1101 and HLA-DPB1*0401 and 0402 molecules. We also demonstrate that peptide NY-ESO-1 87-111 stimulates Th1-type and Th-2/Th0-type CD4(+) T cells and clones when presented in the context of these HLA-DR and HLA-DP4 molecules. Both bulk CD4(+) T cells and CD4(+) T cell clones were capable of recognizing not only peptide-pulsed APCs, but also autologous dendritic cells, either loaded with the NY-ESO-1 protein or transfected with NY-ESO-1 cDNAs. Using IFN-gamma and IL-5 ELISPOT assays and PBL from patients with NY-ESO-1-expressing tumors, we observed the existence of Th1-type circulating CD4(+) T cells recognizing peptide NY-ESO-1 87-111 in the context of HLA-DP4 molecules. Taken together, these data represent the first report of an HLA-DR- and HLA-DP-restricted epitope from a tumor Ag. They also support the relevance of cancer vaccine trials with peptides NY-ESO-1 87-111 in the large number of cancer patients with NY-ESO-1-expressing tumors.
AuthorsMaja Mandic, Florence Castelli, Bratislav Janjic, Christine Almunia, Pedro Andrade, Daniel Gillet, Vladimir Brusic, John M Kirkwood, Bernard Maillere, Hassane M Zarour
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 174 Issue 3 Pg. 1751-9 (Feb 01 2005) ISSN: 0022-1767 [Print] United States
PMID15661941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Epitopes, T-Lymphocyte
  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • HLA-DPw4 antigen
  • HLA-DR Antigens
  • Immunodominant Epitopes
  • Membrane Proteins
  • Peptide Fragments
Topics
  • Alleles
  • Amino Acid Sequence
  • Antibodies, Neoplasm (biosynthesis)
  • Antigen Presentation
  • Antigens, Neoplasm (biosynthesis, immunology, metabolism)
  • CD4-Positive T-Lymphocytes (immunology, metabolism)
  • Clone Cells
  • Dendritic Cells (immunology, metabolism)
  • Epitopes, T-Lymphocyte (blood, immunology, metabolism)
  • Female
  • HLA-DP Antigens (immunology, metabolism)
  • HLA-DP beta-Chains
  • HLA-DR Antigens (immunology, metabolism)
  • Humans
  • Immunodominant Epitopes (blood, immunology, metabolism)
  • Lymphocyte Activation (immunology)
  • Male
  • Melanoma (immunology, metabolism)
  • Membrane Proteins (biosynthesis, immunology, metabolism)
  • Molecular Sequence Data
  • Peptide Fragments (immunology, metabolism)
  • Protein Binding (immunology)
  • Th2 Cells (immunology, metabolism)

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