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Clin Immunol. 2014 May-Jun;152(1-2):1-9. doi: 10.1016/j.clim.2014.02.004. Epub 2014 Feb 19.

T cell epitope mimicry between Sjögren's syndrome Antigen A (SSA)/Ro60 and oral, gut, skin and vaginal bacteria.

Author information

1
Center for Immunity Inflammation and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
2
Center for Immunity Inflammation and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, USA; Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.
3
Center for Immunity Inflammation and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, USA; Division of Rheumatology, Department of Medicine, University of Virginia, Charlottesville, VA, USA; Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA, USA.
4
Center for Immunity Inflammation and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, USA; Department of Pharmacology, University of Virginia, Charlottesville, VA, USA. Electronic address: umesh-deshmukh@omrf.org.

Abstract

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 Sjögren's syndrome.

KEYWORDS:

Microbiota; Molecular mimicry; Ro60/SSA; SLE; Sjögren's syndrome; T epitopes

PMID:
24576620
PMCID:
PMC4004658
DOI:
10.1016/j.clim.2014.02.004
[Indexed for MEDLINE]
Free PMC Article

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