An HLA-DRB1*0402 derived peptide (HV3 65-79) prevents collagen-induced arthritis in HLA-DQ8 transgenic mice.
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| 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 DRB 1*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 DRB 1*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.
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| Authors | P Das, D S Bradley, A Geluk, M M Griffiths, H S Luthra, C S David |
| Journal | Human immunology (Hum Immunol) Vol. 60 Issue 7 Pg. 575-82 (Jul 1999) ISSN: 0198-8859 [Print] United States |
| PMID | 10426274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.) |
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