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Published on: February 5, 2015
Long-term human coronavirus-myelin cross-reactive T-cell clones derived from multiple sclerosis patients
Annie Boucher1, Marc Desforges, Pierre Duquette
1Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, 531, boulevard des Prairies, Laval (Québec), Canada H7V 1B7.
Abstract:
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.
Insights
Human coronaviruses (HCoV) may trigger multiple sclerosis (MS) through molecular mimicry. This study identified cross-reactive T-cells between HCoV and myelin antigens in MS patients, suggesting a potential role in disease initiation or relapses.
Area of Science:
- Immunology
- Neuroscience
- Virology
Background:
- Multiple sclerosis (MS) pathogenesis involves genetic and environmental factors.
- Murine coronaviruses induce MS-like disease, implicating human coronaviruses (HCoV) as potential environmental triggers.
- Previous work identified HCoV-229E/myelin basic protein (MBP) cross-reactive T-cell lines in MS patients.
Purpose of the Study:
- To investigate the molecular basis of antigenic cross-reactivity between HCoV and myelin antigens in MS.
- To identify specific T-cell clones (TCC) involved in HCoV/myelin cross-reactivity.
Main Methods:
- In vitro selection of 155 long-term T-cell clones (TCC) from 32 MS patients using MBP, proteolipid protein (PLP), or HCoV strains (229E, OC43).
- Characterization of TCC specificity (virus-specific, myelin-specific, or cross-reactive).
- RACE RT-PCR amplification and sequencing of Vbeta chains and CDR3 regions in cross-reactive TCC.
Main Results:
- Out of 155 TCC, 114 were virus-specific, 31 were myelin-specific, and 10 demonstrated HCoV/myelin cross-reactivity.
- Cross-reactive TCC were identified in MS patients, with virus-specific and myelin-specific TCC also found in healthy donors.
- Sequencing confirmed clonality and identified the CDR3 region associated with cross-reactivity in ten HCoV/myelin cross-reactive TCC.
Conclusions:
- Findings support the hypothesis of molecular mimicry between coronaviruses and myelin in MS.
- This mimicry may play a role in the initiation or relapse of multiple sclerosis.
- Further investigation into HCoV and myelin cross-reactivity offers insights into MS pathogenesis.
