HUMAN CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX TRANSGENE PREVENTS VIRUS-INDUCED DEMYELINATION IN SUSCEPTIBLE MUTANT B10.D2DML 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 demyelination and TMEV persistence. B10.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 with normal complementation of H-2D region genes. We tested whether expression of a class 1 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.