PMID: 7547689Apr 1, 1995Paper

The protein tyrosine kinase p56lck regulates TCR expression and T cell selection

International Immunology
P O Ericsson, H S Teh

Abstract

The role of the protein tyrosine kinase (PTK), p56lck, in T cell development was evaluated by mating TCR transgenic mice with transgenic mice that expressed lckF505, a constitutively activated form of p56lck which is under the control of the lck proximal promoter element. The TCR transgenic mice expressed either a receptor specific for the male antigen presented by Db (H-Y TCR) or a receptor specific for pigeon cytochrome c peptide presented by I-Ek class II MHC molecules (AND TCR). The lckF505 transgene caused lower TCR expression in immature CD4+CD8+ thymocytes from normal and TCR transgenic mice. Consistent with the conclusion that activated p56lck causes lower TCR expression, the PTK inhibitor, herbimycin A, was able to restore TCR expression to normal levels in CD4+CD8+ thymocytes from TCR/lckF505 doubly transgenic mice. However, despite lower TCR expression, calcium mobilization was only moderately reduced in CD4+CD8+ thymocytes from H-Y TCR/lckF505 doubly transgenic mice. Furthermore, negative selection of CD4+CD8+ thymocytes expressing the H-Y TCR occurred efficiently in H-Y TCR/lckF505 doubly transgenic male mice despite lower TCR levels. By contrast, analysis of H-Y TCR/lckF505 and AND TCR/lckF505 doubly transgenic mi...Continue Reading

Citations

Apr 3, 2001·The Journal of Experimental Medicine·C Schmedt, A Tarakhovsky
Jan 1, 1996·Annual Review of Immunology·G AndersonE J Jenkinson
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·L A SmythD Kioussis
Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·C P LiuP Marrack
Sep 10, 1998·The Journal of Cell Biology·R D SoedeE Roos
Jan 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·P A TrobridgeS D Levin
Jun 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marina von EssenCarsten Geisler

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