title: Promiscuous Recognition of a Trypanosoma cruzi CD8+ T Cell Epitope among HLA-A2, HLA-A24 and HLA-A1 Supertypes in Chagasic Patients.
abstract: BACKGROUND
  TcTLE is a nonamer peptide from Trypanosoma cruzi KMP-11 protein that is conserved among different parasite strains and that is presented by different HLA-A molecules from the A2 supertype. Because peptides presented by several major histocompatibility complex (MHC) supertypes are potential targets for immunotherapy, the aim of this study was to determine whether MHC molecules other than the A2 supertype present the TcTLE peptide.
  
  
  RESULTS
  From 36 HLA-A2-negative chagasic patients, the HLA-A genotypes of twenty-eight patients with CD8+ T cells that recognized the TcTLE peptide using tetramer (twenty) or functional (eight) assays, were determined. SSP-PCR was used to identify the A locus and the allelic variants. Flow cytometry was used to analyze the frequency of TcTLE-specific CD8+ T cells, and their functional activity (IFN-γ, TNFα, IL-2, perforin, granzyme and CD107a/b production) was induced by exposure to the TcTLE peptide. All patients tested had TcTLE-specific CD8+ T cells with frequencies ranging from 0.07-0.37%. Interestingly, seven of the twenty-eight patients had HLA-A homozygous alleles: A*24 (5 patients), A*23 (1 patient) and A*01 (1 patient), which belong to the A24 and A1 supertypes. In the remaining 21 patients with HLA-A heterozygous alleles, the most prominent alleles were A24 and A68. The most common allele sub-type was A*2402 (sixteen patients), which belongs to the A24 supertype, followed by A*6802 (six patients) from the A2 supertype. Additionally, the A*3002/A*3201 alleles from the A1 supertype were detected in one patient. All patients presented CD8+ T cells producing at least one cytokine after TcTLE peptide stimulation.
  
  
  CONCLUSIONS
  These results show that TcTLE is a promiscuous peptide that is presented by the A24 and A1 supertypes, in addition to the A2 supertype, suggesting its potential as a target for immunotherapy.
authors.affiliation: Laboratorio de Parasitología Molecular, Pontificia Universidad Javeriana, Bogotá, Colombia.|Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, Bogotá, Colombia.|Instituto de Parasitología y Biomedicina López-Neyra, CSIC, PTS-Granada, Granada, España.
authors.forename: Paola
authors.initials: P
authors.lastname: Lasso
authors.affiliation: Laboratorio de Parasitología Molecular, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Lina
authors.initials: L
authors.lastname: Beltrán
authors.affiliation: Núcleo de Biotecnología Curauma (NBC), Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.
authors.forename: Fanny
authors.initials: F
authors.lastname: Guzmán
authors.affiliation: Instituto de Arritmias Joseph Brugada, Fundación Clínica Abood Shaio, Bogotá, Colombia.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rosas
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, PTS-Granada, Granada, España.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Thomas
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, PTS-Granada, Granada, España.
authors.forename: Manuel Carlos
authors.initials: MC
authors.lastname: López
authors.affiliation: Grupo de Ciencias Básicas Médicas, Facultad de Medicina, Universidad de los Andes, Bogotá, Colombia.
authors.forename: John Mario
authors.initials: JM
authors.lastname: González
authors.affiliation: Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cuéllar
authors.affiliation: Laboratorio de Parasitología Molecular, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Concepción J
authors.initials: CJ
authors.lastname: Puerta
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D017951:Antigen Presentation / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005838:Genotype; D015788:HLA-A1 Antigen / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D059871:HLA-A24 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D010455:Peptides; D015800:Protozoan Proteins