| First Author | Ling S | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 9 | Pages | 6359-67 |
| PubMed ID | 17947714 | Mgi Jnum | J:152985 |
| Mgi Id | MGI:4360573 | Doi | 10.4049/jimmunol.179.9.6359 |
| Citation | Ling S, et al. (2007) The rheumatoid arthritis shared epitope triggers innate immune signaling via cell surface calreticulin. J Immunol 179(9):6359-67 |
| abstractText | The shared epitope (SE), carried by the vast majority of rheumatoid arthritis patients, is a 5-aa sequence motif in the third allelic hypervariable region of the HLA-DRbeta chain. We have recently demonstrated that the SE acts as an allele-specific ligand that triggers NO-mediated pro-oxidative signaling in opposite cells. The identity of the cell surface molecule that interacts with the SE is unknown. Using affinity chromatography purification, cell-binding assays, surface plasmon resonance, and time-resolved fluorescence resonance energy transfer techniques, we have identified cell surface calreticulin (CRT) as the SE-binding molecule. SE-triggered signaling could be blocked by anti-CRT Abs or Abs against CD91 and by CRT-specific antisense or small-interfering RNA oligonucleotides. Embryonic fibroblasts from crt(-/-) or CD91-deficient mice failed to transduce SE-triggered signals. Exogenously added soluble CRT attached to the cell surface and restored SE-triggered signaling responsiveness in crt(-/-) cells. These data indicate that cell surface CRT, a known innate immunity receptor, which has been previously proposed as a culprit in autoimmunity, plays a critical role in SE-triggered signal transduction. |
