T-cell receptors and collagen induced arthritis in h-2r mice

Marie M. Griffiths, Barry C. Cole, Jun Ito, D. Scott Harper, Gary D. Anderson, Grant W. Cannon, Harvinder S. Luthra, Chella S. David

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Mouse strains BIO, B10.RIII, RIIIS/J and the Fl and backcross progeny arising from them were tested for susceptibility to porcine type II collagen-induced arthritis (PII-CIA). The clinically severe arthritis of rapid onset that is characteristic of PII-immunized B10.RIII mice developed predominantly in hybrid offspring that had inherited at least one copy of wild type T cell receptor (TCR) genes (Vβb genotype) from the B10 or B10.RIII parent. The results indicate that, in the development of PII-CIA, mice expressing the H-2r/r haplotype preferentially utilize TCR Vp genes that are normally encoded within the TCR Vβ genomic deletion region of RIIIS mice (Vβc). After aggressive immunization with PII, the use of alternative TCR Vβ genes, encoded outside of the RIIIS deletion region, produced a high IgG antibody response that was cross-reactive with mouse type II collagen (MII) and equivalent to that of B10.RIII mice, but only a very mild, late onset arthritis of 56% (27/48) incidence in RIIIS male mice and 28% (10/35) incidence in RIIIS female mice. In comparison, B10.RIII mice routinely developed early onset of PII-CIA of significantly higher incidence (100%; p<0.005) and four-fold greater severity, even after milder immunization protocols. The data are compatible with the proposal that the clinically weak CIA response of RIIIs mice may be primarily antibody driven while the severe CIA of B10.RIII mice reflects the added inflammatory effects of collagen-reactive effector-T cells in the joint. The apparent concordance of TCR Vβ utilization in the murine T cell response to MAM (a superantigen produced by M. arthritidis), to MIS-Ia (a retroviral superantigen). and to homologous type II collagen is discussed.

Original languageEnglish (US)
Pages (from-to)221-229
Number of pages9
JournalAutoimmunity
Volume14
Issue number3
DOIs
StatePublished - Jan 1 1993

Keywords

  • Arthritis
  • Collagen
  • Mice
  • Superantigens
  • T cell receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Griffiths, M. M., Cole, B. C., Ito, J., Harper, D. S., Anderson, G. D., Cannon, G. W., Luthra, H. S., & David, C. S. (1993). T-cell receptors and collagen induced arthritis in h-2r mice. Autoimmunity, 14(3), 221-229. https://doi.org/10.3109/08916939309077369