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Master's Dissertation
DOI
10.11606/D.5.2006.tde-12042006-164408
Document
Author
Full name
Juliana Mattos de Almeida Bessa
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2005
Supervisor
Committee
Guglielmi, Luiza Guilherme (President)
Abdallah, Kald Ali
Goldberg, Anna Carla Renata Krepel
Title in Portuguese
"Determinação de alvos antigênicos na doença reumática cardíaca utilizando phage display"
Keywords in Portuguese
Biblioteca de peptídeos
Febre reumática/imunologia
Mimetismo molecular
Streptococcus pyogenes
Abstract in Portuguese
Pacientes com doença reumática cardíaca (DRC) desenvolvem lesões valvares mediadas por linfócitos T CD4+, capazes de reconhecer cruzadamente proteínas cardíacas e estreptocócicas pelo mecanismo de mimetismo molecular. Neste trabalho empregamos uma biblioteca peptídica de Phage Display para identificar auto-antígenos cardíacos capazes de serem reconhecidos por duas linhagens intralesionais de linfócitos T e um clone derivado de uma das linhagens isolados de pacientes com DRC. A análise dos peptídeos dos fagos em banco de dados de proteínas revelou novos epitopos da miosina cardíaca, laminina, vimentina e outras proteínas coiled-coil, provavelmente involvidos no processo auto-imune da DRC. Outras moléculas inflamatórias como citocinas, integrinas e fatores de crescimento também foram identificadas
Title in English
Identification of molecular markers involved in the pathogenesis of rheumatic heart disease by phage display
Keywords in English
Molecular mimicry
Peptide library
Rheumatic fever/immunology
Streptococcus pyogenes
Abstract in English
Rheumatic heart disease (RHD) patients develop valvar lesions with CD4+ T lymphocytes infiltrating the heart. Molecular mimicry between streptococcal and cardiac proteins recognized by these T cells may explain these auto-aggressive lesions. In the present work we used a Phage Display peptide library to identify cardiac antigens which could be recognized by two heart infiltrate T cell lines and by a T cell clone derived from one of the lines which were isolated from RHD patients. Using the protein data bank to analyse the phage peptides, we observed that many sequences showed homology with cardiac myosin, laminin, vimentin and other coiled-coil proteins, suggesting the involvement of these proteins in the autoimmune process of RHD. Other inflammatory molecules such as cytokines and integrins were also identified
 
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Publishing Date
2006-04-13
 
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