No requirement for p56lck in the antigen-stimulated clonal deletion of thymocytes.
Activation of protein-tyrosine kinases (PTKs) is required for signal transduction during T cell activation, although the pathway used during thymic selection is unknown. An in vitro system was established in which T cell receptor transgenic thymocytes underwent clonal deletion in response to peptide antigen. The effects of two PTK-specific inhibitors, herbimycin A and genistein, on the clonal deletion of immature thymocytes and the activation of mature thymocytes were examined. Clonal deletion occurred while T cell activation was inhibited and when no p56lck activity was evident. Thus, p56lck is not required for the antigen-stimulated step of clonal deletion of immature thymocytes, and negative selection proceeds via a distinct pathway.
Nakayama
K
K
Howard Hughes Medical Institute, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Loh
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DY
D000818:Animals; D016227:Benzoquinones; D002478:Cells, Cultured; D002645:Chickens; D004261:DNA Replication; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D007739:L Cells; D047029:Lactams, Macrocyclic; D008213:Lymphocyte Activation / Q000187:drug effects; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014162:Transfection
D016227:Benzoquinones; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011809:Quinones; D011948:Receptors, Antigen, T-Cell; D017828:Rifabutin; C020754:herbimycin; D010047:Ovalbumin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)