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H-2 Antigens pp 735-745 | Cite as

H-2 Genes in TMEV-Induced Demyelination, A Model for Multiple Sclerosis

  • Roger W. Melvold
  • Diane M. Jokinen
  • Stephen D. Miller
  • Mauro C. Dal Canto
  • Howard L. Lipton
Part of the NATO ASI Series book series (NSSA, volume 144)

Abstract

Theiler’s murine encephalomyelitis virus (TMEV) is a natural enteric pathogen of mice which, upon entry into the CNS, sets up a persistent infection that, in some strains of mice, results in an immunologically-mediated, progressive chronic demyelinating disease with histopathological and clinical similarities to human multiple sclerosis. Although the CNS virus infection persists in all strains, only some go on to develop the demyelinating disease. This susceptibility has a strong genetic basis which involves both H-2 and non-H-2 loci. Comparisons involving different combinations of susceptible and resistant strains indicate the involvement of numerous loci, not all of which are apparent in any given comparison. The differences between the susceptible DBA/2J and resistant C57BL/6 and C57BL/10 strains are primarily dependent upon H-2 genotype and at least one non-H-2 gene, with resistance being dominant to susceptibility. The D region of H-2 has a strong influence (H-2 b associated with resistance and H-2 d with susceptibility) and substitution, in appropriate hybrids, of single gene mutations of the H-2D b gene abrogates resistance. This may mean that resistance is, in fact, an active process mediated, for example, by specific suppression.

In DBA/2, the H-2 d haplotype is associated with susceptibility, unlike the H-2 identical, but resistant, BALB/c strain. The resistance associated with H-2 b is not absolute and can, in segregating populations be overcome by the non-H-2 genome. It is likely that critical combinations of genes, e.g. those encoding H-2 and the T cell receptor chains, are the determining factors in disease susceptibility or resistance.

Keywords

Multiple Sclerosis Demyelinating Disease Susceptible Strain Mononuclear Cell Infiltration Single Gene Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Roger W. Melvold
    • 1
  • Diane M. Jokinen
    • 1
  • Stephen D. Miller
    • 1
  • Mauro C. Dal Canto
    • 2
    • 3
  • Howard L. Lipton
    • 3
  1. 1.Department of Microbiology-Immunology and the Cancer CenterNorthwestern University Medical and Dental SchoolsChicagoUSA
  2. 2.Department of PathologyNorthwestern University Medical and Dental SchoolsChicagoUSA
  3. 3.Department of NeurologyNorthwestern University Medical and Dental SchoolsChicagoUSA

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