HLA-DQ6/8 double transgenic mice develop auricular chondritis following type II collagen immunization

A model for human relapsing polychondritis

David S. Bradley, Pritam Das, Marie M. Griffiths, Harvinder S. Luthra, Chella S. David

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

We have generated transgenic (tg) mice expressing HLA-DQ8αβ (DQA1*0301/DQB*0302) or HLA-DQ6αβ (DQA1*0103/DQB1*0601) molecules lacking endogenous murine class II expression (Aβ0) to investigate the ability of these HLA class II to present type II Collagen (CII) and induce collagen-induced arthritis. The DQ8αβ tg mice responded strongly to CII, developing severe arthritis, while DQ6αβ tg mice were nonresponsive to CII. The addition of the mixed haplotype DQ8α6β molecule did not significantly influence CII reactivity. To examine the interaction of DQ6αβ and DQ8αβ molecules in vivo, we generated double tg DQ6αβ/8αβ (Aβ0) mice expressing both the α- and β-chains of DQ6 and DQ8 molecules by mating DQαβ (Aβ0) and DQ8αβ (Aβ0) tg mice. CII-immunized DQ6αβ/8αβ tg mice developed severe experimental polychondritis, exhibiting both polyarthritis and auricular chondritis. The clinical, serologic, and histologic manifestations of experimental polychondritis are similar to those symptoms in human relapsing polychondritis. The susceptibility of DQ6αβ/8αβ tg mice compared with resistance in the parental strains suggests that expression of both the DQ6αβ and DQ8αβ tgs, unique to the DQ6αβ8αβ tg strain, is important in susceptibility to experimental polychondritis. The DQ6αβ/8αβ tg mice provide a model to investigate putative autoantigens and the mechanisms of pathogenesis involved in relapsing polychondritis as well as the influence of the expression of multiple HLA class II molecules on the disease process.

Original languageEnglish (US)
Pages (from-to)5046-5053
Number of pages8
JournalJournal of Immunology
Volume161
Issue number9
StatePublished - Nov 1 1998

Fingerprint

Relapsing Polychondritis
Collagen Type II
Transgenic Mice
Immunization
Arthritis
Experimental Arthritis
Autoantigens
HLA-DQ6 antigen
Haplotypes

ASJC Scopus subject areas

  • Immunology

Cite this

HLA-DQ6/8 double transgenic mice develop auricular chondritis following type II collagen immunization : A model for human relapsing polychondritis. / Bradley, David S.; Das, Pritam; Griffiths, Marie M.; Luthra, Harvinder S.; David, Chella S.

In: Journal of Immunology, Vol. 161, No. 9, 01.11.1998, p. 5046-5053.

Research output: Contribution to journalArticle

Bradley, David S. ; Das, Pritam ; Griffiths, Marie M. ; Luthra, Harvinder S. ; David, Chella S. / HLA-DQ6/8 double transgenic mice develop auricular chondritis following type II collagen immunization : A model for human relapsing polychondritis. In: Journal of Immunology. 1998 ; Vol. 161, No. 9. pp. 5046-5053.
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