The role of C5 and T-cell receptor Vb genes in susceptibility to collagen-induced arthritis

Dominic G. Spinella, John R. Jeffers, Robert A. Reife, John Stuart

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Abstract

Collagen-induced arthritis (CIA) is a rodent arthritis model in which immunization with heterologous type II collagen induces an inflammatory polyarthritis. Susceptibility to the disease is mediated by major histocompatibility complex (MHC) genes as well as genes at other loci. Previous studies of the SWR/J mouse strain, which is resistant to CIA despite bearing the susceptible H-2q haplotype, have suggested that this resistance is the result of a deletion of T-cell receptor (Tcr) Vb gene segments which is carried by this strain. Other studies have implicated a deficiency in complement component C5 as the cause for the resistance. In order to assess the relative importance of these two genes in susceptibility to CIA, and to provide an estimate of the number of independent genes involved in the disease, we analyzed 196 F2 progeny of a (DBA/1 × SWR/J) cross for arthritis susceptibility, and expression of both C5 and Tcr genes. Thirty of the F2 progeny developed arthritis. All of the arthritic mice had at least one copy of the wild-type C5 allele, while the Tcr-Vb haplotypes were distributed in Mendelian fashion. These results demonstrate that C5 sufficiency is an absolute requirement for CIA, but that Tcr-Vb genes located within the SWR deletion have little influence. Genetic analysis of the incidence rate suggests that there is polygenic control of susceptibility to CIA and that in addition to H-2, 5-6 other independent loci (including C5) may be involved.

Original languageEnglish (US)
Pages (from-to)23-27
Number of pages5
JournalImmunogenetics
Volume34
Issue number1
DOIs
StatePublished - Jul 1 1991

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T-Cell Receptor Genes
Experimental Arthritis
Arthritis
Haplotypes
Genes
Complement C5
Collagen Type II
Disease Susceptibility
T-Cell Antigen Receptor
Major Histocompatibility Complex
Rodentia
Immunization
Alleles
Incidence

All Science Journal Classification (ASJC) codes

  • Immunology
  • Genetics

Cite this

The role of C5 and T-cell receptor Vb genes in susceptibility to collagen-induced arthritis. / Spinella, Dominic G.; Jeffers, John R.; Reife, Robert A.; Stuart, John.

In: Immunogenetics, Vol. 34, No. 1, 01.07.1991, p. 23-27.

Research output: Contribution to journalArticle

Spinella, Dominic G. ; Jeffers, John R. ; Reife, Robert A. ; Stuart, John. / The role of C5 and T-cell receptor Vb genes in susceptibility to collagen-induced arthritis. In: Immunogenetics. 1991 ; Vol. 34, No. 1. pp. 23-27.
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