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...
Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 133(2009), 1 vom: 01. Okt., Seite 145-53 |
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1. Verfasser: | |
Weitere Verfasser: | , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2009
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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... |
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 |
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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 |