Identification of multiple HLA-A*0201-restricted cruzipain and FL-160 CD8+ epitopes recognized by T cells from chronically Trypanosoma cruzi-infected patients.
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.
Fonseca
Simone G
SG
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.
Moins-Teisserenc
Hélène
H
Clave
Emmanuel
E
Ianni
Bárbara
B
Nunes
Vera Lopes
VL
Mady
Charles
C
Iwai
Leo K
LK
Sette
Alessandro
A
Sidney
John
J
Marin
Maria Lúcia C
ML
Goldberg
Anna Carla
AC
Guilherme
Luiza
L
Charron
Dominique
D
Toubert
Antoine
A
Kalil
Jorge
J
Cunha-Neto
Edecio
E
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*
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