The protein tyrosine kinase p56ICK regulates TCR expression and T cell selection
- 1 April 1995
- journal article
- research article
- Published by Oxford University Press (OUP) in International Immunology
- Vol. 7 (4) , 617-624
- https://doi.org/10.1093/intimm/7.4.617
Abstract
The role of the protein tyrosine kinase (PTK), p56Ick, In T cell development was evaluated by mating TCR transgenic mice with transgenic mice that expressed ICKF505, a constitutively activated form of p56ICK which is under the control of the ICK 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 plgeon cytochrome c peptide presented by I-Ek class II MHC molecules (AND TCR). The ICKF505 transgene caused lower TCR expression in immature CD4+CD8+ thymocytes from normal and TCR transgenic mice. Consistent with the conclusion that activated p56ICK causes lower TCR expression, the PTK inhibitor, herbimycin A, was able to restore TCR expression to normal levels in CD4+CD8+ thymocytes from TCR/ICKF505 doubly transgenic mice. However, despite lower TCR expression, calcium mobilization was only moderately reduced in CD4+CD8+ thymocytes from H-Y TCR/ICKF505 doubly transgenic mice. Furthermore, negative selection of CD4+CD8+ thymocytes expressing the H-Y TCR occurred efficiently in H-Y TCR/ICKF505 doubly transgenic male mice despite lower TCR levels. By contrast, analysis of H-Y TCR/ICKF505 and AND TCR/ICKF505 doubly transgenic mice showed that positive selection in these mice was reduced by 4- to 5-fold by the ICKF505 transgene. The smaller proportion of cells that were positively selected in doublytransgenic ICKF505 mice expressed normal levels of TCR but higher levels of the appropriate CD4or CD8 co-receptor molecule. These results indicate that the positive selection of thymocytes is regulated by the enzymatic activity of p56ICKKeywords
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