Spontaneous inflammatory disease in HLA-B27 transgenic mice is independent of MHC class II molecules: A direct role for B27 heavy chains and not B27-derived peptides

Sanjay D. Khare, Michael J. Bull, Julie Hanson, Harvinder S. Luthra, Chella S. David

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Although association of HLA-B27 with human spondyloarthropathies has been known for several years, its role in disease pathogenesis is not understood. Recently, a few investigators have proposed that presentation of B27-derived peptides by MHC class II molecules may be the underlying mechanism. HLA-B27 transgenic rat and mouse models have provided a new tool for understanding the exact role of B27 in disease pathogenesis. HLA-B27 mice lacking endogenous β2-microglobulin (B27+β2m°) develop disease after they are transferred from the barrier facility to the conventional colony. This model was utilized to test the hypothesis that B27-derived peptide presented by MHC class II molecules is the cause of the disease. The MHC class II knockout gene, Aβ°, was bred into our B27+β2m°mice, and disease manifestation was monitored. These mice develop spontaneous disease, demonstrating that MHC class II molecules do not play a major role in B27- related disease. Thus, the disease is not manifested by presentation of B27- derived peptides by class II molecules, since these mice are devoid of H2-A and H2-E molecules. Furthermore, in vivo treatment with mAb against the heavy chain of B27 reduced the incidence of disease in B27+β2m°mice. Our results clearly demonstrate that B27 heavy chains are directly involved in the disease process.

Original languageEnglish (US)
Pages (from-to)101-106
Number of pages6
JournalJournal of Immunology
Volume160
Issue number1
StatePublished - Jan 1 1998

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HLA-B27 Antigen
Transgenic Mice
Peptides
Transgenic Rats
Spondylarthropathies
MHC Class II Genes
Research Personnel

ASJC Scopus subject areas

  • Immunology

Cite this

Spontaneous inflammatory disease in HLA-B27 transgenic mice is independent of MHC class II molecules : A direct role for B27 heavy chains and not B27-derived peptides. / Khare, Sanjay D.; Bull, Michael J.; Hanson, Julie; Luthra, Harvinder S.; David, Chella S.

In: Journal of Immunology, Vol. 160, No. 1, 01.01.1998, p. 101-106.

Research output: Contribution to journalArticle

Khare, Sanjay D. ; Bull, Michael J. ; Hanson, Julie ; Luthra, Harvinder S. ; David, Chella S. / Spontaneous inflammatory disease in HLA-B27 transgenic mice is independent of MHC class II molecules : A direct role for B27 heavy chains and not B27-derived peptides. In: Journal of Immunology. 1998 ; Vol. 160, No. 1. pp. 101-106.
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