title: HLA-DP4 expression and immunity to NY-ESO-1: correlation and characterization of cytotoxic CD4+ CD25- CD8- T cell clones.
abstract: NY-ESO-1 is one of the most immunogenic cancer antigens known to date, eliciting spontaneous immune responses in approximately 50% of patients with NY-ESO-1+ cancers. Spontaneous CD4+ and CD8+ T cell responses were found in patients with detectable NY-ESO-1 serum antibody, indicating an integrated type of immune response induced by NY-ESO-1+ malignancies. A close association between spontaneous NY-ESO-1 immunity and the HLA-DP4 allele was suggested in a recent study. To address these results, we assessed the NY-ESO-1 antibody and HLA-DP4 status of 102 patients with NY-ESO-1+ malignancies. However, no correlation between HLA-DP4 and NY-ESO-1 immunity was found. To explore the role of HLA-DP4-restricted CD4+ T cells in cancer immunity, we established HLA-DP4- restricted NY-ESO-1-specific CD4+ T cell clones by limiting dilution and repeated stimulation with NY-ESO-1 peptide p157-170 from NY-ESO-1 seropositive patients. A subset of CD4+ T cell clones was reactive with naturally processed NY-ESO-1 presented by autologous DCs that were pulsed with recombinant NY-ESO-1 protein, lysates of NY-ESO-1-expressing tumor cell lines, or transduced with recombinant NY-ESO-1 viral constructs in ELISPOT assays. Three different CD4+ T cell clones were used to mediate the specific lysis of allogeneic HLA-DP4+ Epstein-Barr virus-transformed B cells (EBV-B) pulsed with NY-ESO-1 p157-170. The Th1 phenotype and effector functions of the CD4+ T cell clones described here provide an important rationale for the activation of antigen-specific CD4+ T cells along with CD8+ T cells in cancer vaccination strategies.
authors.affiliation: II. Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Huarte
authors.forename: Julia
authors.initials: J
authors.lastname: Karbach
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Armin
authors.initials: A
authors.lastname: Bender
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.forename: Michael
authors.initials: M
authors.lastname: Arand
authors.forename: Djordje
authors.initials: D
authors.lastname: Atanackovic
authors.forename: Jonathan
authors.initials: J
authors.lastname: Skipper
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Alexander
authors.initials: A
authors.lastname: Knuth
authors.forename: Elke
authors.initials: E
authors.lastname: Jäger
mesh_terms: D000938:Antigen-Presenting Cells / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry* / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002999:Clone Cells / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology / Q000502:physiology; D006682:HLA-DP Antigens / Q000096:biosynthesis* / Q000235:genetics; D059868:HLA-DP beta-Chains; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry* / Q000502:physiology*
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C056284:HLA-DPw4 antigen; D008565:Membrane Proteins; D015375:Receptors, Interleukin-2