title: NY-ESO-1 encodes DRB1*0401-restricted epitopes recognized by melanoma-reactive CD4+ T cells.
abstract: The NY-ESO-1 gene is expressed by a range of human tumors and encodes HLA-A2-restricted melanoma peptides recognized by CD8+ CTLs. Here we report that the NY-ESO-1 gene also encodes two overlapping, but non-cross-reactive, HLA-DRB1*0401-presented peptides that are recognized by CD4+ T cells. The NY-ESO-1(119-143) peptide was able to induce specific CD4+ T cells in vitro from both an HLA-DRB1*0401+ normal donor and an HLA-DRB1*0401+ patient with melanoma. Bulk and cloned CD4+ T cells produced IFN-gamma specifically in response to, and also lysed, T2.DR4 cells pulsed with peptide NY-ESO-1(119-143) and the autologous tumor cell line, but not a DRB1*0401+ melanoma cell line that does not express NY-ESO-1. Interestingly, the NY-ESO119-143 peptide contains two overlapping putative "core" epitopes recognized by non-cross-reactive anti-NY-ESO-1(119-143) CD4+ T-cell clones. Taken together, these data support the use of this novel DR4-restricted tumor peptide, NY-ESO-1(119-143), or its two "sub-epitopes" in immunotherapeutic trials designed to generate or enhance specific CD4+ T-cell responses against tumors expressing NY-ESO-1 in vivo.
authors.affiliation: Department of Medicine and Melanoma Center, University of Pittsburgh Cancer Institute, Pennsylvania 15213, USA. zarourhm@msx.upmc.edu
authors.forename: H M
authors.initials: HM
authors.lastname: Zarour
authors.forename: W J
authors.initials: WJ
authors.lastname: Storkus
authors.forename: V
authors.initials: V
authors.lastname: Brusic
authors.forename: E
authors.initials: E
authors.lastname: Williams
authors.forename: J M
authors.initials: JM
authors.lastname: Kirkwood
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015804:HLA-DR4 Antigen / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D008565:Membrane Proteins; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins