T-cell molecular mimicry in Chagas disease: identification and partial structural analysis of multiple cross-reactive epitopes between Trypanosoma cruzi B13 and cardiac myosin heavy chain

T-cell molecular mimicry in Chagas disease: identification and partial structural analysis of multiple cross-reactive epitopes between Trypanosoma cruzi B13 and cardiac myosin heavy chain

Author Iwai, L. K. Google Scholar
Juliano, M. A. Google Scholar
Juliano, L. Google Scholar
Kalil, J. Google Scholar
Cunha-Neto, E. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Chagas disease cardiornyopathy (CCC) is one of the few examples of post-infectious autoimmunity, where infectious episodes with an established pathogen, the protozoan parasite Trypanosoma cruzi, clearly triggers molecular mimicry-related target organ immune damage. CD4(+) T-cell clones infiltrating hearts from CCC patients cross-reactively recognize human cardiac myosin, the major heart protein, and the immunodominam B 13 protein from T. cruzi. Moreover, in vitro priming with B 13 leads to the recovery of cardiac myosin cross-reactive T-cell clones. in order to identify cross-reactive epitopes between B 13 protein and human cardiac myosin, we used B13 peptide S15.4, preferentially recognized by CCC patients, to establish a T-cell clone from an HLA-DQ7 individual. the B13 S15.4 peptide- specific CD4(+) T-cell clone 3E5 was tested in proliferation assays against 15 Lys/His-substituted S15.4-derived peptides for TCR/HLA contact analysis. Together with previous HLA-binding data and molecular modeling of the HLA-DQ7-peptide S15.4 complex, Lys/His scanning analysis showed eight TCR/HLA contact positions. Clone 3E5 was also tested against 45 15-mer peptides from human beta-cardiac myosin heavy chain bearing the central HLA-DQ7 binding motif. Clone 3135 recognized 13 peptides from cardiac myosin. the alignment of cross-reactive peptides in cardiac myosin showed very limited sharing of residues or side chains with similar chemical/structural features at aligned positions, indicative of a very degenerate TCR recognition pattern. the existence of degenerate intramolecular recognition, with multiple low-homology, cross-reactive epitopes in a single autoantigenic protein may have implications in increasing the magnitude of the autoimmune response in CCC and other autoimmune diseases. (c) 2005 Elsevier B.V. All rights reserved.
Keywords B13 protein
Chagas disease cardiomyopathy
human cardiac myosin
T-cell molecular mimicry
Trypanosoma cruzi
Language English
Date 2005-03-01
Published in Journal of Autoimmunity. London: Academic Press Ltd Elsevier B.V., v. 24, n. 2, p. 111-117, 2005.
ISSN 0896-8411 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 111-117
Origin http://dx.doi.org/10.1016/j.jaut.2005.01.006
Access rights Closed access
Type Article
Web of Science ID WOS:000228781200004
URI http://repositorio.unifesp.br/handle/11600/28179

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