title: Evaluation of IFN-gamma production by CD8 T lymphocytes in response to the K1 peptide from KMP-11 protein in patients infected with Trypanosoma cruzi.
abstract: The cellular response mediated by MHC class I restricted CD8+ T cells has been shown to be crucial in the control of Chagas disease. The K1 peptide derived from T. cruzi KMP-11 protein has a high binding affinity to the HLA-A*0201 molecule. Nevertheless, it is not known whether this peptide is processed and displayed as an MHC class I epitope during natural infection by T. cruzi. The aim of this study was to evaluate, by ELISPOT assay, the ability of K1 peptide to activate CD8+ T lymphocytes to produce IFN-gamma. Therefore, CD8+ T lymphocytes from 22 HLA-A*0201+ individuals, 12 chronic chagasic patients and 10 uninfected controls, were analysed. The results revealed that two of the chagasic patients had IFN-gamma-secreting CD8+ T cells that were able to respond to K1 peptide with a relative frequency of 110 and 230 per million CD8+ T cells. In contrast, none of HLA-A*0201+ uninfected controls responded to K1 peptide. Responses to HLA-A*0201 restricted peptide from the influenza matrix protein were found in six chagasic patients and four uninfected controls with an average frequency of 175 and 111 cells per million CD8+ T cells, respectively. Moreover, a flow cytometric assay for degranulation showed that chagasic responders had K1-specific cytotoxic CD8+ T cells. It is shown here for the first time that the K1 peptide is efficiently processed, presented and recognized by CD8+ T lymphocytes during the natural course of Chagas disease.
authors.affiliation: Laboratorio de Parasitología Molecular, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: H
authors.initials: H
authors.lastname: Diez
authors.forename: M C
authors.initials: MC
authors.lastname: López
authors.forename: M
authors.initials: M
authors.lastname: Del Carmen Thomas
authors.forename: F
authors.initials: F
authors.lastname: Guzmán
authors.forename: F
authors.initials: F
authors.lastname: Rosas
authors.forename: V
authors.initials: V
authors.lastname: Velazco
authors.forename: J M
authors.initials: JM
authors.lastname: González
authors.forename: C
authors.initials: C
authors.lastname: Puerta
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000276:immunology / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D015800:Protozoan Proteins; C090009:kinetoplastid membrane protein 11, Leishmania donovani; D007371:Interferon-gamma