Influence of Deletion of T Cell Receptor V_β Genes on the Theiler's Virus Model of Multiple Sclerosis

Abstract

To determine the role of TCR V_β genes in a model of multiple sclerosis (MS), we studied Theiler's virus infection in congenic mice with deletion of TCR V_β chromosome. Congenic mice expressing the V^a_β [50% deletion of TCR V_β] or V^c_β 70% deletion of TCR V_β] haplotype were generated in mice resistant [B10 (H-2^b)], intermediate [B10.K (H-2^k), B10.RIII (H-2^r)] or susceptible [B10.S (H-2^s), and B10.Q (H-2^q)] to Theiler's virus induced demyelination. Deletion of TCR V_β genes (V^a_β or V^c_β) did not convert B10 or B10.K congenic mice to susceptibility. In contrast, congenic B10.RIII-V^c_β developed prominent demyelination and 10-to 100-fold increase in virus-antigen expression in spinal cord compared to B10.RIII mice. No effect on the extent of demyelination was observed in B10.S-V^a_β, B10.S-V^c_β or B10.Q-V^c_β mice. These experiments illustrate the critical interactions between MHC, TCR, and background genes in susceptibility to immune-mediated disease.

Key Words:

• Demyelination
• Myelin
• Oligodendrocyte
• Immunopathology
• Picornavirus
• Major Histocompatibility Complex