title: Identification of multiple HLA-A*0201-restricted cruzipain and FL-160 CD8+ epitopes recognized by T cells from chronically Trypanosoma cruzi-infected patients.
abstract: Chronic Chagas disease occurs in 16 million individuals chronically infected by the protozoan Trypanosoma cruzi in Latin America, and may lead to a dilated cardiomyopathy in 10-30% of patients. A vigorous cellular immune response holds parasitism in check. However, up to now, few T. cruzi proteins have been shown to be recognized by CD8+ T cells from Chagas disease patients. In this study, we designed 94 peptides derived from T. cruzi proteins cruzipain and FL-160, predicted to bind to HLA-A2 molcules. After in vitro binding assays to HLA-A*0201, 26 peptides were selected, and their recognition by PBMC from Chagas disease patients was tested with the IFN-gamma ELISPOT assay. All 26 peptides were recognized by PBMC from at least one patient. Furthermore, a tetrameric HLA-A*0201 complex built with the cruzipain 60-68 peptide that was frequently recognized in the periphery also bound to CD8+ T cells from a heart-infiltrating T cell line obtained from a single patient with Chagas disease cardiomyopathy. Thus, our results suggest that the recognition of CD8+ T cell epitopes in cruzipain and FL-160 may have a pathogenic or protective role in chronic Chagas disease.
authors.affiliation: Laboratório de Imunologia, Heart Institute, Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, Av Dr Enéas de Carvalho Aguiar, 44 BL 2, 9 andar, São Paulo-SP 05403-000, Brazil.
authors.forename: Simone G
authors.initials: SG
authors.lastname: Fonseca
authors.forename: Hélène
authors.initials: H
authors.lastname: Moins-Teisserenc
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Clave
authors.forename: Bárbara
authors.initials: B
authors.lastname: Ianni
authors.forename: Vera Lopes
authors.initials: VL
authors.lastname: Nunes
authors.forename: Charles
authors.initials: C
authors.lastname: Mady
authors.forename: Leo K
authors.initials: LK
authors.lastname: Iwai
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Maria Lúcia C
authors.initials: ML
authors.lastname: Marin
authors.forename: Anna Carla
authors.initials: AC
authors.lastname: Goldberg
authors.forename: Luiza
authors.initials: L
authors.lastname: Guilherme
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D014355:Chagas Disease / Q000276:immunology / Q000469:parasitology; D002908:Chronic Disease; D003546:Cysteine Endopeptidases / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D015800:Protozoan Proteins; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides; D015800:Protozoan Proteins; C069805:FL-160 antigen, Trypanosoma cruzi; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C063214:cruzipain