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Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655
The Tec family tyrosine kinase Itk is critical for efficient
signaling downstream of the TCR. Biochemically, Itk is directly
phosphorylated and activated by Lck. Subsequently, Itk activates
phospholipase C-
1, leading to calcium mobilization and extracellular
signal-regulated kinase/mitogen-activated protein kinase activation.
These observations suggested that Itk might play an important role in
positive selection and CD4/CD8 lineage commitment during T cell
development in the thymus. To test this, we crossed Itk-deficient mice
to three lines of TCR transgenics and analyzed progeny on three
different MHC backgrounds. Analysis of these mice revealed that fewer
TCR transgenic T cells develop in the absence of Itk. In addition,
examination of multiple T cell development markers indicates that
multiple stages of positive selection are affected by the absence of
Itk, but the T cells that do develop appear normal. In contrast to the
defects in positive selection, CD4/CD8 lineage commitment seems to be
intact in all the TCR transgenic
itk-/- lines tested. Overall, these
data indicate that altering TCR signals by the removal of Itk does not
affect the appropriate differentiation of thymocytes based on their MHC
specificity, but does impact the efficiency with which thymocytes
complete their maturation process.
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