Differential Expression of H-2K and H-2D in the Central Nervous System of Mice Infected with Theiler's Virus

Ayse Altintas, Zeiling Cai, Larry R. Pease, Moses Rodriguez

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36 Scopus citations


A model of demyelination induced by Theiler's murine encephalomyelitis virus (TMEV) was used to study differential regulation of class I MHC gene products in the brain and spinal cord of resistant (B10) and susceptible (B10.Q and B10.RBQ) mice. Allelic polymorphisms in the H-2D region, but not the H-2K region, play a primary role in determining susceptibility to late demyelinating disease. However, even though significant structural diversity distinguishes class I alleles, there are no discernible K or D-specific patterns of structural diversity within the peptide binding domains of these glycoproteins. Our hypothesis was that D region association of susceptibility to demyelination was related to differences in the expression of the K and D Ag in the central nervous system (CNS) after TMEV infection. Using allele-specific mAb and an immunoperoxidase technique, we demonstrated transient but equivalent increases in K and D Ag expression in the brain and spinal cord of resistant mice beginning 7 days after TMEV infection, which returned to baseline by 90 days. However, when genetically susceptible animals were examined, a significantly greater increase in D expression relative to K expression was seen in the brain and spinal cord at all post-infection observation periods. Immunosuppression of genetically resistant animals before TMEV infection, which results in viral persistence, was accompanied by equivalent increases in both the K and D Ag. Depletion of CD81 T cells, but not CD4 + T cells, in susceptible mice ablated class I expression in the CNS in response to TMEV infection, implying that CD8 + cells contribute to the differential regulation of K and D Ag in the CNS. These findings are consistent with the hypothesis that differences in gene regulation may account for different roles of the K and D loci play in determining resistance and susceptibility to TMEV-induced demyelinating disease.

Original languageEnglish (US)
Pages (from-to)2803-2812
Number of pages10
JournalJournal of Immunology
Issue number5
StatePublished - 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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