Lauritsen J P, Christensen M D, Dietrich J, Kastrup J, Odum N, Geisler C
Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute, Denmark.
J Immunol. 1998 Jul 1;161(1):260-7.
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 p56(lck) and p59(fyn) but independent of PKC and the CD3gamma leucine-based (L-based) internalization motif. In contrast, PKC-induced TCR down-regulation is dependent on the CD3gamma L-based internalization motif but independent of p56(lck) and p59(fyn). Finally, our data indicate that in the absence of TCR ligation, TCR expression levels can be finely regulated via the CD3gamma 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.
TCR下调在T细胞发育过程中和成熟T细胞中调节T细胞反应方面发挥着重要作用。TCR的下调是由特定配体与TCR结合和/或蛋白激酶C（PKC）激活所诱导的。我们在此报告，配体和PKC诱导的TCR下调是由两种不同的独立机制介导的。配体诱导的TCR下调依赖于蛋白酪氨酸激酶p56(lck)和p59(fyn)，但不依赖于PKC和基于CD3γ亮氨酸的（L基序）内化基序。相反，PKC诱导的TCR下调依赖于基于CD3γ L基序的内化基序，但不依赖于p56(lck)和p59(fyn)。最后，我们的数据表明，在没有TCR连接的情况下，TCR表达水平可通过PKC和丝氨酸/苏氨酸蛋白磷酸酶活性之间的平衡，经由基于CD3γ L基序进行精细调节。这种不依赖TCR连接的TCR表达水平调节在确定T细胞与抗原呈递细胞相遇时的激活阈值方面可能很重要。
