Critical residues on HLA-DRB1*0402 HV3 peptide for HLA-DQ8-restricted immunogenicity: implications for rheumatoid arthritis predisposition.

摘要: Recently, we have proposed that the combination of HLA-DQ and -DR alleles is responsible for association HLA class II region with rheumatoid arthritis (RA). According to this model, some alleles, namely DQ4, DQ7, DQ8, DQ9, predispose carriers severe RA, but a self peptide sequence KDILEDERAAVDTYC from third hypervariable (HV3) DRB1 including DRB1*0402, can protect disease if presented by DQ molecules. This model implies DQ9 should be able present set common peptides, despite polymorphisms in their Ag binding groove. In study, further analyzed immunogenicity DRB1*0402 HV3 DQ8-transgenic mice. We found motif DERAA guarantees DQ8-restricted immunogenicity, R main anchor residue DQ. Interestingly, p1 pocket probably controls identical all four RA-associated Our results imply RA DR subtypes explained linkage displaying site similar "arthritogenic" peptides.