Long-term human coronavirus-myelin cross-reactive T-cell clones derived from multiple sclerosis patients.
Autoimmune reactions associated with MS involve genetic and environmental factors. Because murine coronaviruses induce an MS-like disease, the human coronaviruses (HCoV) are attractive candidates as environmental factors involved in a demyelinating pathology. We previously reported the isolation of HCoV-229E/myelin basic protein (MBP) cross-reactive T-cell lines (TCL) in MS patients. To investigate antigenic cross-reactivity at the molecular level, 155 long-term T-cell clones (TCC) were derived from 32 MS patients by in vitro selection with MBP, proteolipid protein (PLP) or HCoV (strains 229E and OC43). Overall, 114 TCC were virus-specific, 31 were specific for myelin Ag and 10 other were HCoV/myelin cross-reactive. Twenty-eight virus-specific TCC and 7 myelin-specific TCC were obtained from six healthy donors. RACE RT-PCR amplification of the Vbeta chains of five of ten the cross-reactive TCC confirmed clonality and sequencing identified the CDR3 region associated with cross-reactivity. Our findings have promising implications in the investigation of the role of molecular mimicry between coronaviruses and myelin in MS as a mechanism related to disease initiation or relapses.
Boucher
Annie
A
Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, 531, boulevard des Prairies, Laval (Québec), Canada H7V 1B7.
Desforges
Marc
M
Duquette
Pierre
P
Talbot
Pierre J
PJ
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D049109:Cell Proliferation; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D017934:Coronavirus / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037182:T-Cell Antigen Receptor Specificity / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013997:Time Factors
D000956:Antigens, Viral; D000939:Epitopes; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta