title: Three novel NY-ESO-1 epitopes bound to DRB1*0803, DQB1*0401 and DRB1*0901 recognized by CD4 T cells from CHP-NY-ESO-1-vaccinated patients.
abstract: Three novel NY-ESO-1 CD4 T cell epitopes were identified using PBMC obtained from patients who were vaccinated with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1). The restriction molecules were determined by antibody blocking and using various EBV-B cells with different HLA alleles as APC to present peptides to CD4 T cells. The minimal epitope peptides were determined using various N- and C-termini truncated peptides deduced from 18-mer overlapping peptides originally identified for recognition. Those epitopes were DRB1*0901-restricted NY-ESO-1 87-100, DQB1*0401-restricted NY-ESO-1 95-107 and DRB1*0803-restricted NY-ESO-1 124-134. CD4 T cells used to determine those epitope peptides recognized EBV-B cells or DC that were treated with recombinant NY-ESO-1 protein or NY-ESO-1-expressing tumor cell lysate, suggesting that the epitope peptides are naturally processed. These CD4 T cells showed a cytokine profile with Th1 characteristics. Furthermore, NY-ESO-1 87-100 peptide/HLA-DRB1*0901 tetramer staining was observed. Multiple Th1-type CD4 T cell responses are beneficial for inducing effective anti-tumor responses after NY-ESO-1 protein vaccination.
authors.affiliation: Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mizote
authors.forename: Taku
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Kei
authors.initials: K
authors.lastname: Tanaka
authors.forename: Midori
authors.initials: M
authors.lastname: Isobe
authors.forename: Hisashi
authors.initials: H
authors.lastname: Wada
authors.forename: Takashi
authors.initials: T
authors.lastname: Saika
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kita
authors.forename: Yukari
authors.initials: Y
authors.lastname: Koide
authors.forename: Akiko
authors.initials: A
authors.lastname: Uenaka
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nakayama
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D016056:Immunodominant Epitopes; D009363:Neoplasm Proteins; D011994:Recombinant Proteins