期刊
CLINICAL IMMUNOLOGY
卷 152, 期 1-2, 页码 1-9出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2014.02.004
关键词
Sjiogren's syndrome; SLE; Ro60/SSA; Molecular mimicry; T epitopes; Microbiota
类别
资金
- National Institutes of Health, USA [R01-A1079621, R01-AR047988, R01-AR049449]
This study was undertaken to test the hypothesis that Sjogren's syndrome Antigen A (SSA)/Ro60-reactive T cells are activated by peptides originating from oral and gut bacteria. T cell hybridomas generated from HLA-DR3 transgenic mice recognized 3 regions on Ro60, with core epitopes mapped to amino acids 228-238, 246-256 and 371-381. BLAST analysis identified several mimicry peptides, originating from human oral, intestinal, skin and vaginal bacteria, as well as environmental bacteria. Amongst these, a peptide from the von Willebrand factor type A domain protein (vWFA) from the oral microbe Capnocytophaga ochracea was the most potent activator. Further, Ro60-reactive T cells were activated by recombinant vWFA protein and whole Escherichia coli expressing this protein. These results demonstrate that peptides derived from normal human microbiota can activate Ro60-reactive T cells. Thus, immune responses to commensal microbiota and opportunistic pathogens should be explored as potential triggers for initiating autoimmunity in SLE and SjOgren's syndrome.. (C) 2014 Elsevier Inc. All rights reserved.
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