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). 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.
Tang
Bo
B
Department of Medicine, University of Tennessee, Memphis TN, 38163, USA.
Zhou
Jing
J
Park
Jeoung-Eun
JE
Cullins
David
D
Yi
Ae-Kyung
AK
Kang
Andrew H
AH
Stuart
John M
JM
Myers
Linda K
LK
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D024043:Collagen Type II / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000494:pharmacology*; D010766:Phosphorylation / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000819:agonists*; D015398:Signal Transduction / Q000276:immunology; D013267:Stilbenes / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D000072377:Syk Kinase; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism
D024043:Collagen Type II; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell; D013267:Stilbenes; D013449:Sulfonamides; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases