Effects of the major histocompatibility complex loci and T-cell receptor beta-chain repertoire on Theiler's virus-induced demyelinating disease

We have investigated the potential effects of H-2 and T-cell receptor (TCR) Vβ family genes on induction of T-cell immunity and susceptibility to virally induced demyelinating disease by using BALB.S (H-2K^SA ^SD^S) and BALB.S3R (H-2K^SA^SD ^d/L^d) mice. These parameters were compared with those of highly susceptible SJL/J (H-2K^SA^SD^S) mice that contain only one-half of TCR Vβ family genes compared with the above-mentioned strains. Our results demonstrate that BALB.S but not BALB.S3R mice are susceptible similar to SJL/J mice. Although the level of CD4 ⁺ T-cell infiltration to the CNS was elevated in susceptible mice, virus-specific immune responses restricted with H-2^S were similar in these mice. No preferential use of Vβ families associated with differences in the major histocompatibility complex (MHC) components was apparent. However, the pattern and sequence of CDR3 distribution shows T-cell clonal accumulation in the CNS associated with the H-2 components. Further anti-CD8 antibody treatment of resistant BALB.S3R mice abrogated resistance to demyelinating disease, indicating that CD8⁺ T cells restricted with H-2D ^d/L^d are most likely to exert resistance in BALB.S3R mice. These studies indicated that TCR Vβ and MHC class II genes are the secondary to a particular MHC class I gene expression in susceptibility to virally induced demyelinating disease.