T cell epitope characterization in tandemly repetitive Trypanosoma cruzi B13 protein

T cell epitope characterization in tandemly repetitive Trypanosoma cruzi B13 protein

Author Abel, LCJ Google Scholar
Iwai, L. K. Google Scholar
Viviani, W. Google Scholar
Bilate, A. M. Google Scholar
Fae, K. C. Google Scholar
Ferreira, R. C. Google Scholar
Goldberg, A. C. Google Scholar
Juliano, L. Google Scholar
Juliano, M. A. Google Scholar
Ianni, B. Google Scholar
Mady, C. Google Scholar
Gruber, A. Google Scholar
Hammer, J. Google Scholar
Sinigaglia, F. Google Scholar
Kalil, J. Google Scholar
Cunha-Neto, E. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Proteins containing tandemly repetitive sequences are present in several immunodominant protein antigens in pathogenic protozoan parasites. the tandemly repetitive Ttypanosoma cruzi B13 protein is recognized by IgG antibodies from 98% of Chagas' disease patients. Little is known about the molecular mechanisms that lead to the immunodominance of the repeated sequences, and there is limited information on T cell epitopes in such repetitive antigens. We finely characterized the T cell recognition of the tandemly repetitive, degenerate B13 protein by T cell lines, clones and PBMC from Chagas' disease cardiomyopathy (CCC), asymptomatic T cruzi infected (ASY) and non-infected individuals (N). PBMC proliferative responses to recombinant B 13 protein were restricted to individuals bearing HLA-DQA1*0501 (DQ7),-DR1, and -DR2; B13 peptides bound to the same HLA molecules in binding assays. the HLA-DQ7-restricted minimal T cell epitope [FGQAAAG(D/E)KP] was identified with an overlapping combinatorial peptide library including all B13 sequence variants in T cruzi Y strain B13 protein; the underlined small residues (G) under barQ (A) under bar were the major HLA contact residues. Among natural B 13 15-mer variant peptides, molecular modeling showed that several variant positions were solvent (TCR)-exposed, and substitutions at exposed positions abolished recognition. While natural B13 variant peptide S15.9 seems to be the immunodominant epitope for Chagas' disease patients, S15.4 was preferentially recognized by CCC rather than ASY patients, which may be pathogenically relevant. This is the first thorough characterization of T cell epitopes of a tandemly repetitive protozoan antigen and may suggest a role for T cell help in the immunodominance of protozoan repetitive antigens. (c) 2005 Elsevier SAS. All rights reserved.
Keywords T cell epitope
B13 protein
Trypanosoma cruzi
tandemly repetitive proteins
immunodominant antigens
Language English
Date 2005-08-01
Published in Microbes and Infection. Amsterdam: Elsevier B.V., v. 7, n. 11-12, p. 1184-1195, 2005.
ISSN 1286-4579 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1184-1195
Origin http://dx.doi.org/10.1016/j.micinf.2005.03.033
Access rights Closed access
Type Article
Web of Science ID WOS:000233099800002
URI http://repositorio.unifesp.br/handle/11600/28409

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