title: T cell epitope mimicry between Sjögren's syndrome Antigen A (SSA)/Ro60 and oral, gut, skin and vaginal bacteria.
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.
authors.affiliation: Center for Immunity Inflammation and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szymula
authors.affiliation: Center for Immunity Inflammation and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Rosenthal
authors.affiliation: Center for Immunity Inflammation and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Szczerba
authors.affiliation: 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.
authors.forename: Harini
authors.initials: H
authors.lastname: Bagavant
authors.affiliation: 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.
authors.forename: Shu Man
authors.initials: SM
authors.lastname: Fu
authors.affiliation: 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.
authors.forename: Umesh S
authors.initials: US
authors.lastname: Deshmukh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D002206:Capnocytophaga / Q000235:genetics / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015803:HLA-DR3 Antigen / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007422:Intestines / Q000382:microbiology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018716:Molecular Mimicry / Q000276:immunology*; D009055:Mouth / Q000382:microbiology; D010455:Peptides / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*; D012867:Skin / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology; D014621:Vagina / Q000382:microbiology; D014841:von Willebrand Factor / Q000235:genetics / Q000276:immunology; D000099207:SS-A Antigen
chemical_list: D018984:Epitopes, T-Lymphocyte; D015803:HLA-DR3 Antigen; D010455:Peptides; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D014841:von Willebrand Factor; D000099207:SS-A Antigen
keywords: Microbiota; Molecular mimicry; Ro60/SSA; SLE; Sjögren's syndrome; T epitopes