The Src family kinase Fyn mediates signals induced by TCR antagonists.
FcR nonbinding anti-CD3 epsilon mAbs elicit partial TCR signaling that leads to T cell unresponsiveness and tolerance in vivo. In this study, the membrane-proximal events that promote T cell inactivation by FcR nonbinding anti-CD3 mAbs were examined. In the context of FcR nonbinding anti-CD3, TCR complexes did not aggregate and failed to translocate into glycolipid-enriched membrane microdomains. Furthermore, FcR nonbinding anti-CD3 mAbs induced tyrosine phosphorylation of the Fyn substrate Cbl, but not the ZAP-70 substrate linker for activation of T cells. Overexpression of Fyn, but not Lck, restored the mitogenicity of FcR nonbinding anti-CD3 in primary T cells. Taken together, these results suggest that Fyn mediates the partial signaling induced by TCR antagonists.
Tang
Qizhi
Q
The Diabetes Center, University of California, San Francisco, CA 94143, USA.
Subudhi
Sumit K
SK
Henriksen
Kammi J
KJ
Long
Catherine G
CG
Vives
Franklin
F
Bluestone
Jeffrey A
JA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000502:physiology; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050721:Proto-Oncogene Proteins c-cbl; D051076:Proto-Oncogene Proteins c-fyn; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D014161:Transduction, Genetic; D044767:Ubiquitin-Protein Ligases
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D011518:Proto-Oncogene Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; C493849:Cbl protein, mouse