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Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute, Copenhagen, Denmark
TCR down-regulation plays an important role in modulating T cell
responses both during T cell development and in mature T cells.
Down-regulation of the TCR is induced by engagement of the TCR by
specific ligands and/or by activation of protein kinase C (PKC). We
report here that ligand- and PKC-induced TCR down-regulation is
mediated by two distinct, independent mechanisms. Ligand-induced TCR
down-regulation is dependent on the protein tyrosine kinases
p56lck and p59fyn but
independent of PKC and the CD3
leucine-based (L-based)
internalization motif. In contrast, PKC-induced TCR down-regulation is
dependent on the CD3 L-based internalization motif but independent
of p56lck and p59fyn.
Finally, our data indicate that in the absence of TCR ligation, TCR
expression levels can be finely regulated via the CD3 L-based motif
by the balance between PKC and serine/threonine protein phosphatase
activities. Such a TCR ligation-independent regulation of TCR
expression levels could probably be important in determining the
activation threshold of T cells in their encounter with APC.
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