title: HLA class I - associated immunodominance affects CTL responsiveness to an ESO recombinant protein tumor antigen vaccine.
abstract: OBJECTIVE
  Vaccination with full-length human tumor antigens aims at inducing or increasing antitumor immune responses, including CD8 CTL in cancer patients across the HLA barrier. We have recently reported that vaccination with a recombinant tumor-specific NY-ESO-1 (ESO) protein, administered with Montanide and CpG resulted in the induction of specific integrated antibody and CD4 T cell responses in all vaccinated patients examined, and significant CTL responses in half of them. Vaccine-induced CTL mostly recognized a single immunodominant region (ESO 81-110). The purpose of the present study was to identify genetic factor(s) distinguishing CTL responders from nonresponders.
  
  
  METHODS
  We determined the HLA class I alleles expressed by CTL responders and nonresponders using high-resolution molecular typing. Using short overlapping peptides spanning the ESO immunodominant CTL region and HLA class I/ESO peptide tetramers, we determined the epitopes recognized by the majority of vaccine-induced CTL.
  
  
  RESULTS
  CTL induced by vaccination with ESO protein mostly recognized distinct but closely overlapping epitopes restricted by a few frequently expressed HLA-B35 and HLA-Cw3 alleles. All CTL responders expressed at least one of the identified alleles, whereas none of the nonresponders expressed them.
  
  
  CONCLUSIONS
  Expression of HLA-B35 and HLA-Cw3 is associated with the induction of immunodominant CTL responses following vaccination with recombinant ESO protein. Because recombinant tumor-specific proteins are presently among the most promising candidate anticancer vaccines, our findings indicate that the monitoring of cancer vaccine trials should systematically include the assessment of HLA association with responsiveness.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U892, CLCC René Gauducheau, Saint Herblain, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Bioley
authors.forename: Philippe
authors.initials: P
authors.lastname: Guillaume
authors.forename: Immanuel
authors.initials: I
authors.lastname: Luescher
authors.forename: Alice
authors.initials: A
authors.lastname: Yeh
authors.forename: Bo
authors.initials: B
authors.lastname: Dupont
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: Gregory
authors.initials: G
authors.lastname: Mears
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D015797:HLA-B35 Antigen / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D015797:HLA-B35 Antigen; D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D008565:Membrane Proteins; D014614:Vaccines, Synthetic