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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoimmunity / immunology
  • Capnocytophaga / genetics
  • Capnocytophaga / immunology
  • Cross Reactions / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • HLA-DR3 Antigen / immunology
  • Humans
  • Hybridomas / immunology
  • Intestines / microbiology
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Molecular Mimicry / immunology*
  • Mouth / microbiology
  • Peptides / genetics
  • Peptides / immunology
  • Recombinant Proteins / immunology
  • Ribonucleoproteins / immunology*
  • Sjogren's Syndrome / immunology*
  • Skin / microbiology
  • T-Lymphocytes / immunology
  • Vagina / microbiology
  • von Willebrand Factor / genetics
  • von Willebrand Factor / immunology

Substances

  • Epitopes, T-Lymphocyte
  • HLA-DR3 Antigen
  • Peptides
  • Recombinant Proteins
  • Ribonucleoproteins
  • SS-A antigen
  • von Willebrand Factor