Identification of HLA-A*0201-restricted cytotoxic T-cell epitopes of Trypanosoma cruzi TcP2beta protein in HLA-transgenic mice and patients.
Trypanosoma cruzi-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of parasite growth and will play an important part in therapeutic and prophylactic T. cruzi vaccines. The identification of parasite-specific epitopes that are efficiently recognized by CTLs is the first step in the development of future vaccines. HLA-A2 transgenic mice (HHD) were shown to provide a powerful model for studying the induction of HLA-A*0201-restricted immune responses in vivo, since these mice are endowed with a CTL repertoire representative of HLA-A2.1 individuals. Here, we describe the immunological characterization of T-cell epitopes of the T. cruzi ribosomal P2 protein (TcP2beta) that are recognized by HLA-A*0201-restricted CTLs in HLA-transgenic mice and humans. Epitopes identified in the present study do not share sequence homology with the homologous human or murine counterparts and so they should not induce any autoreactive response. Moreover, HHD mice vaccinated with these peptide epitopes have reduced parasitemia after challenge with a lethal T. cruzi infection. Hence, these epitopes represent potential subunit components of multi-protein vaccines to prevent Chagas' disease.
Unité d'immunité cellulaire antivirale, Département d'immunologie, Institut Pasteur, 28, rue du Dr-Roux, 75724 cedex 15, Paris, France.
Francisco
F
Garcia
Pilar
P
Sepulveda
Pascale
P
Liegeard
Josiane
J
Gregoire
Emmanuel
E
Hermann
François
F
Lemonnier
Pierre
P
Langlade-Demoyen
Mireille
M
Hontebeyrie
Yu Chun
YC
Lone
D000595:Amino Acid Sequence; D000818:Animals; D014355:Chagas Disease / Q000517:prevention & control; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018512:Parasitemia / Q000517:prevention & control; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D015800:Protozoan Proteins; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology; D012269:Ribosomal Proteins / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C064601:L12E protein, Trypanosoma cruzi; D010455:Peptides; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D012269:Ribosomal Proteins