Human class I major histocompatibility complex transgene prevents virus‐induced demyelination in susceptible mutant B 10.d2^dml mice

Theiler's murine encephalomyelitis virus (TMEV) induces immune‐mediated demyelination in susceptible strains of mice, providing an excellent model for multiple sclerosis. Class I genes within the major histocompatibility complex locus (H‐2D region)play a major role in determining whether strains of mice develop chronic in determining whether strains of mice develop chronic demyelination and TMEV persistence. B 10.D2^dml mice with deletion in the 3′ end of D^d and the 5′ end of L^d genes develop the most prominent demyelination in comparison with resistant B10. D2 mice normal complementation of H‐2D region genes. We tested whether expression of a class I human transgene (HLA‐B27) would modulate virus‐induced demyelination in mutant B10.D2^dml mice. Transgenic B10.D2^dml (HLA‐B27⁺) mice infected with virus showed dramatic decrease in the extent of demyelination (p < 0.0001) and virus antigen expression in spinal cord compared with littermate controls without the human class I transgene. These experiments demonstrate that transgenic expression of a human class I major histocompatibility complex locus molecule can prevent demyelination induced by a virus in mutant mice.