Long-term human coronavirus-myelin cross-reactive T-cell clones derived from multiple sclerosis patients

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.

Figure 1

Typical Ag-specific proliferation profiles in CPM of monospecific myelin or coronavirus TCC established from MS patients or healthy controls. Selection was achieved with HCoV-229E or HCoV-OC43, MBP or PLP Ag. Activated TCC are identified by their name and selecting Ag. The background values of tritiated thymidine intake (CPM) appear for all TCC. Stimulation index (S.I.) are indicated at the top of the figure.