An HLA-DRB1*0402 derived peptide (HV3 65-79) prevents collagen-induced arthritis in HLA-DQ8 transgenic mice

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

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

On the basis of our studies with HLA class II transgenic mice, we had proposed that complementation of HLA-DQ and HLA-DR alleles may determine both disease susceptibility and severity in rheumatoid arthritis (RA). According to our model, certain HLA-DQ alleles, such as HLA-DQ8, predispose individuals to RA, while a self-peptide derived from the third hypervariable region (HV3 65-79) of HLA-DR alleles, such as DRB1*0402, can protect from disease if presented by the DQ molecule. To test this hypothesis, we examined the immunomodulatory effects of the DRB1*0402 derived peptide (HV3 65-79) on collagen-induced arthritis (CIA) in HLA-DQ8 mice. Co-immunization of the DRB1*0402 peptide significantly reduced the severity of arthritis (mean score = 1.5 ± 0.6 vs 5.2 ± 1.4 in controls), whereas multiple doses of the peptide reduced the incidence of disease (3.5% vs 35-60% in controls). Subsequent analysis revealed that the DRB1*0402 peptide mediated protection may be due to the generation of a subset of regulatory cells, which down- regulate collagen-specific pro-inflammatory responses. These results provide additional insights towards understanding the role of MHC class II molecules in RA predisposition.

Original languageEnglish (US)
Pages (from-to)575-582
Number of pages8
JournalHuman Immunology
Volume60
Issue number7
DOIs
StatePublished - Jul 1999

Keywords

  • IL-10
  • MHC
  • Rheumatoid arthritis
  • Shared-epitope
  • TCR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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