Complementation between HLA-DR4 (DRB1*0401) and specific H2-A molecule in transgenic mice leads to collagen-induced arthritis

Shuchong Pan, Veena Taneja, Marie M. Griffiths, Harvinder Luthra, Chella S. David

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

We generated transgenic mice with DRB1*0401 gene with mutation in the β2 domain (aa 110 and 139) for better interaction with mCD4. The DR4 transgene was introduced into H2-A(q) (B10RQB3) and H2-A(f)(B10RFB3) to examine the role of DR4 in collagen arthritis. The HLA-DR molecules in these mice were found to be functional on the basis of their positive/negative selection of the Vβ T cell repertoire. H2-A(q) mice are resistant to porcine CII-induced arthritis. The RQB3/DR4 mice (H2A(q)/DR4) developed severe collagen induced arthritis (CIA) when immunized with Porcine type II collagen while the negative littermates were resistant. RQB3.DR4 mice were also highly susceptible to CIA induced by Human CII while negative littermates got only mild disease. However, RFB3/DR4 mice (H2A(f)/DR4) did not get CIA with any type II collagen. Therefore, the DR4 gene in the context of H2-A(q) predisposes to severe arthritis but not in the context of H2-Af. Antibodies to renatured cyanogen bromide (CB) cleaved fragments of PII in RQB3/DR4 mice and negative littermates suggest that the presence of DR4 does not result in any differences in specificity of antibody response to CB fragments. These results indicate that a specific gene complementation occurring between DR4 and H2.A(q) but not DR4 and H2A(f) promotes the induction of arthritis with PII and HII in these mice. A similar interaction may be involved between DR and DQ molecules in human RA.

Original languageEnglish (US)
Pages (from-to)816-825
Number of pages10
JournalHuman Immunology
Volume60
Issue number9
DOIs
StatePublished - Sep 1999

Keywords

  • In vivo model
  • MHC
  • Rheumatoid arthritis
  • Transgenic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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