An HLA-DRB1*0402 derived peptide (HV3 65-79) prevents collagen-induced arthritis in HLA-DQ8 transgenic mice.
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.
Das
P
P
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Bradley
D S
DS
Geluk
A
A
Griffiths
M M
MM
Luthra
H S
HS
David
C S
CS
D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000453:epidemiology / Q000276:immunology*; D003094:Collagen; D004334:Drug Administration Schedule; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D015994:Incidence; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*
D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553506:HLA-DRB1*04:02 antigen; D010455:Peptides; D016753:Interleukin-10; D003094:Collagen