T cell receptor signaling induced by an analog peptide of type II collagen requires activation of Syk

We have previously described an analog peptide of type II collagen (CII) that can suppress collagen-induced arthritis (CIA). This analog peptide represents CII(245-270), the immunodominant epitope of CII, but with substitutions at 260, 261, and 263 - CII(245-270) (A(260), B(261), and N(263)) (A9). T...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 133(2009), 1 vom: 01. Okt., Seite 145-53
1. Verfasser: Tang, Bo (VerfasserIn)
Weitere Verfasser: Zhou, Jing, Park, Jeoung-Eun, Cullins, David, Yi, Ae-Kyung, Kang, Andrew H, Stuart, John M, Myers, Linda K
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2009
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Collagen Type II Cytokines GATA3 Transcription Factor Gata3 protein, mouse Intracellular Signaling Peptides and Proteins Oligopeptides mehr... Receptors, Antigen, T-Cell Stilbenes Sulfonamides 3,3',4,5'-tetrahydroxystilbene 6KS3LS0D4F Protein-Tyrosine Kinases EC 2.7.10.1 Syk Kinase EC 2.7.10.2 Syk protein, mouse Extracellular Signal-Regulated MAP Kinases EC 2.7.11.24 JNK Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases
Beschreibung
Zusammenfassung:We have previously described an analog peptide of type II collagen (CII) that can suppress collagen-induced arthritis (CIA). This analog peptide represents CII(245-270), the immunodominant epitope of CII, but with substitutions at 260, 261, and 263 - CII(245-270) (A(260), B(261), and N(263)) (A9). To elucidate the mechanisms responsible for suppression, we used mice transgenic for a collagen-specific T cell receptor (TCR). When we found that APCs pulsed with A9 failed to induce T cell phosphorylation of TCR-zeta and ZAP-70, we explored alternative signaling pathways. We determined that A9 instead induced phosphorylation of spleen tyrosine kinase (Syk). The importance of Syk was confirmed by the use of chemical Syk inhibitors, which blocked both cytokine secretion and activation of GATA-3 mediated by peptide A9. In summary, T cells use an alternative pathway in response to A9 that involves Syk. This novel T cell pathway may represent an important means for altering T cell phenotypes
Beschreibung:Date Completed 08.10.2009
Date Revised 20.10.2021
published: Print
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2009.06.006