Collagen-induced arthritis in T cell receptor V beta congenic B10.Q mice.
B10.Q (H-2q) mice congenic for the truncated T cell receptor (TCR) V beta a and V beta c haplotypes were derived to examine the influence of TCR V beta genomic deletions in murine collagen-induced arthritis (CIA). Previous studies using gene complementation and segregation analyses suggested that in SWR (H-2q) mice, possession of the V beta a gene deletion results in CIA resistance. However, other studies have suggested alternative hypotheses. Thus, analysis of TCR V beta congenic mice allows for direct examination of V beta genotypes in CIA control. After immunization with bovine type II collagen, B10.Q-V beta a mice showed no difference in arthritis susceptibility, onset, or severity when compared with prototype B10.Q mice. In contrast, B10.Q-V beta c mice, which lack the V beta 6, 15, 17, and 19 families in addition to the V beta a deletion, were highly resistant to CIA. In vivo depletion of V beta 6+ T cells in B10.Q-V beta a mice significantly delayed arthritis onset suggesting that, among those V beta genes present in V beta a but absent in V beta c, V beta 6+ T cells contribute to arthritogenesis. Our findings show that, in B10.Q-V beta congenic mice, while the V beta a genotype does not prevent CIA, the highly truncated V beta c genotype renders B10.Q mice resistant to CIA. Thus, deletions within the V beta TCR genome can indeed influence CIA and suggests that the TCR repertoire displays only marginal flexibility in response to arthritogenic stimuli.
Nabozny
G H
GH
Department of Immunology, Mayo Graduate School of Medicine, Rochester, Minnesota 55905.
Bull
M J
MJ
Hanson
J
J
Griffiths
M M
MM
Luthra
H S
HS
David
C S
CS
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D003094:Collagen; D004195:Disease Models, Animal; D005434:Flow Cytometry; D017353:Gene Deletion; D005816:Genetic Complementation Test; D006239:Haplotypes; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D003094:Collagen