T-cell receptor Vbeta deletion and Valpha polymorphism are responsible for the resistance of SWR mouse to arthritis induction |
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Authors: | G E Osman Mark C Hannibal Jon P Anderson Saijai Cheunsuk Stephen R Lasky H Denny Liggitt Warren C Ladiges Leroy E Hood |
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Institution: | (1) Department of Molecular Biotechnology, Box 357650, University of Washington School of Medicine, Seattle, WA 98195, USA e-mail: gamal@u.washington.edu, Tel.: +1-206-6857843, Fax: +1-206-5431013, US;(2) Department of Comparative Medicine, University of Washington, School of Medicine, Seattle, WA 98195, USA, US |
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Abstract: | Collagen type II-induced arthritis (CIA) develops in susceptible mouse strains after intradermal injections of type II collagen
(CII) in complete Freund's adjuvant (CFA). Susceptibility to CIA in mice is linked to genes of the major histocompatibility
complex (MHC). Although the SWR mouse has a susceptible MHC haplotype (H2
q
), it is resistant to CIA. SWR exhibits at least two known immunological defects: (1) it contains a germline deletion of about
50% of T-cell receptor (TCR) Vβ-chain gene segments, and (2) SWR is deficient in complement component C5. It has been shown
that T cells that express TCRVα11.1 and TCRVβ8.2 play a substantial role in the pathogenesis of arthritis in the DBA/1 mouse
(H2
q
). We generated SWR transgenic (tg) mice to determine whether the expression of pathogenic Vα11.1 and/or Vβ8.2 transgenes
would confer arthritis susceptibility. Arthritis was induced in the SWR TCRαβ tg mice, but not in SWR TCRβ tg mice. To address
the role of Vα11.1 in arthritis susceptibility, we examined the allelic polymorphisms of the Tcra-V11-gene subfamily members between the arthritis susceptible DBA/1 mouse and the arthritis-resistant SWR mouse strain. The amino
acid sequences of the Vα11.1 alleles differ at two positions (codons 18 and 68). Accordingly, these two amino acid changes are sufficient to allow the
production of pathogenic T cells in SWR mice. This is the first demonstration of the association of a particular Tcra-V allele and arthritis susceptibility in mice.
Received: 20 November 1998 / Revised: 15 February 1999 |
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Keywords: | Animal model Arthritis Autoimmune disease T-cell receptor polymorphism Transgenic mice |
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