Influence of deletion of T cell receptor V beta genes on the Theiler's virus model of multiple sclerosis.
To determine the role of TCR V beta genes in a model of multiple sclerosis (MS), we studied Theiler's virus infection in congenic mice with deletion of TCR V beta chromosome. Congenic mice expressing the V beta a [50% deletion of TCR V beta] or V beta c 70% deletion of TCR V beta] haplotype were generated in mice resistant [B10 (H-2b)], intermediate [B10.K (H-2k), B10.RIII (H-2r)] or susceptible [B10.S (H-2s), and B10.Q (H-2q)] to Theiler's virus induced demyelination. Deletion of TCR V beta genes (V beta a or V beta c) did not convert B10 or B10.K congenic mice to susceptibility. In contrast, congenic B10.RIII-V beta c developed prominent demyelination and 10- to 100-fold increase in virus-antigen expression in spinal cord compared to B10.RIII mice. No effect on the extent of demyelination was observed in B10.S-V beta a, B10.S-V beta c or B10.Q-V beta c mice. These experiments illustrate the critical interactions between MHC, TCR, and background genes in susceptibility to immune-mediated disease.
Rodriguez
M
M
Mayo Clinic/Foundation, Dept. of Immunology, Rochester, MN 55905, USA.
Nabozny
G H
GH
Thiemann
R L
RL
David
C S
CS
D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis; D003433:Crosses, Genetic; D003711:Demyelinating Diseases / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D017353:Gene Deletion; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013116:Spinal Cord / Q000276:immunology; D017945:Theilovirus / Q000276:immunology*
D000956:Antigens, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta