T cell receptor signaling induced by an analog peptide of type II collagen requires activation of Syk
| Autor: | David L. Cullins, Andrew H. Kang, John M. Stuart, Linda K. Myers, Ae-Kyung Yi, Jeoung-Eun Park, Jing Zhou, Bo Tang |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
T cell Immunology Receptors Antigen T-Cell Antigen-Presenting Cells Syk Mice Transgenic chemical and pharmacologic phenomena GATA3 Transcription Factor Biology p38 Mitogen-Activated Protein Kinases Article Mice Stilbenes medicine Animals Syk Kinase Immunology and Allergy Phosphorylation Extracellular Signal-Regulated MAP Kinases Antigen-presenting cell Collagen Type II Sulfonamides T-cell receptor Intracellular Signaling Peptides and Proteins JNK Mitogen-Activated Protein Kinases hemic and immune systems Tyrosine-Protein Kinase SYK Protein-Tyrosine Kinases Arthritis Experimental Molecular biology medicine.anatomical_structure Mice Inbred DBA Cytokines Cytokine secretion Signal transduction Oligopeptides Signal Transduction |
| Zdroj: | Clinical Immunology. 133:145-153 |
| ISSN: | 1521-6616 |
| Popis: | 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-ζ 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. |
| Databáze: | OpenAIRE |
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