Recognition of conserved amino acid motifs of common viruses and its role in autoimmunity.
The triggers of autoimmune diseases such as multiple sclerosis (MS) remain elusive. Epidemiological studies suggest that common pathogens can exacerbate and also induce MS, but it has been difficult to pinpoint individual organisms. Here we demonstrate that in vivo clonally expanded CD4+ T cells isolated from the cerebrospinal fluid of a MS patient during disease exacerbation respond to a poly-arginine motif of the nonpathogenic and ubiquitous Torque Teno virus. These T cell clones also can be stimulated by arginine-enriched protein domains from other common viruses and recognize multiple autoantigens. Our data suggest that repeated infections with common pathogenic and even nonpathogenic viruses could expand T cells specific for conserved protein domains that are able to cross-react with tissue-derived and ubiquitous autoantigens.
Sospedra
Mireia
M
Cellular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Zhao
Yingdong
Y
zur Hausen
Harald
H
Muraro
Paolo A
PA
Hamashin
Christa
C
de Villiers
Ethel-Michele
EM
Pinilla
Clemencia
C
Martin
Roland
R
D000595:Amino Acid Sequence; D001327:Autoimmune Diseases / Q000276:immunology / Q000821:virology; D015551:Autoimmunity; D017124:Conserved Sequence; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D008969:Molecular Sequence Data; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000821:virology; D022783:Torque teno virus / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D011948:Receptors, Antigen, T-Cell