Identification of the rheumatoid arthritis shared epitope binding site on calreticulin.

ABSTRACT:

Background

The rheumatoid arthritis (RA) shared epitope (SE), a major risk factor for severe disease, is a five amino acid motif in the third allelic hypervariable region of the HLA-DRbeta chain. The molecular mechanisms by which the SE affects susceptibility to--and severity of--RA are unknown. We have recently demonstrated that the SE acts as a ligand that interacts with cell surface calreticulin (CRT) and activates innate immune signaling. In order to better understand the molecular basis of SE-RA association, here we have undertaken to map the SE binding site on CRT.

Principal findings

Surface plasmon resonance (SPR) experiments with domain deletion mutants suggested that the SE binding site is located in the P-domain of CRT. The role of this domain as a SE-binding regio

SUBMITTER: Ling S 

PROVIDER: S-EPMC2908537 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature