| Autor: |
Steenbakkers PG; Department of Pharmacology, N. V. Organon, Oss, The Netherlands. peter.steembakkers@organon.com, Baeten D, Rovers E, Veys EM, Rijnders AW, Meijerink J, De Keyser F, Boots AM |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Jun 01; Vol. 170 (11), pp. 5719-27. |
| DOI: |
10.4049/jimmunol.170.11.5719 |
| Abstrakt: |
Recently human cartilage gp-39 (HC gp-39) was identified as a candidate autoantigen in rheumatoid arthritis (RA). To further investigate the relevance of this Ag in RA, we have generated a set of five mAbs to a combination epitope of complexes of HC gp-39(263-275) and the RA-associated DR alpha beta 1*0401 HLA class II molecules. FACS studies revealed that these mAb recognize specific complexes on homozygous DR alpha beta 1*0401-positive B lymphoblastoid cells pulsed with HC gp-39(263-275). The best mAb, 12A, was further characterized using a set of irrelevant DR alpha beta 1*0401-binding peptides and truncated/elongated versions of HC gp-39(263-275) itself. The minimal epitope recognized in combination with DR alpha beta 1*0401 was HC gp-39(263-273). Peptides not encompassing HC gp-39(263-273) were not recognized. Three of five mAb were able to inhibit (up to 90%) the response of HC gp-39(263-275)-specific DR alpha beta 1*0401-restricted T cell hybridomas to peptide-pulsed APC or purified complexes. Using mAb 12A, we have been able to identify and localize dendritic cells that present DR alpha beta 1*0401/HC gp-39(263-275) complexes in synovial tissue of DR alpha beta 1*0401-positive RA patients, indicating local presentation of the HC gp-39(263-275) epitope in the inflamed target tissue by professional APC. These data support a role of HC gp-39 in the local autoimmune response that leads to chronic inflammation and joint destruction. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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