Dietrich J, Geisler C
Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute, DK-2200 Copenhagen, Denmark.
J Biol Chem. 1998 Oct 9;273(41):26281-4. doi: 10.1074/jbc.273.41.26281.
The leucine-based motif in the T cell receptor (TCR) subunit CD3gamma constitutes a strong internalization signal. In fully assembled TCR this motif is inactive unless phosphorylated. In contrast, the motif is constitutively active in CD4/CD3gamma and Tac/CD3gamma chimeras independently of phosphorylation and leads to rapid internalization and sorting of these chimeras to lysosomal degradation. Because the TCRzeta chain rescues incomplete TCR complexes from lysosomal degradation and allows stable surface expression of fully assembled TCR, we addressed the question whether TCRzeta has the potential to mask the CD3gamma leucine-based motif. By studying CD4/CD3gamma and CD16/CD3gamma chimeras, we found that CD16/CD3gamma chimeras associated with TCRzeta. The CD16/CD3gamma-TCRzeta complexes were stably expressed at the cell surface and had a low spontaneous internalization rate, indicating that the leucine-based motif in these complexes was inactive. In contrast, the CD4/CD3gamma chimeras did not associate with TCRzeta, and the leucine-based motif in these chimeras was constitutively active resulting in a high spontaneous internalization rate and low expression of the chimeras at the cell surface. Thus, our data demonstrate that TCRzeta allows stable cell surface expression of receptors containing CD3gamma leucine-based motifs by its potential to mask such motifs.
T细胞受体（TCR）亚基CD3γ中基于亮氨酸的基序构成一个强大的内化信号。在完全组装的TCR中，除非磷酸化，该基序是无活性的。相反，在CD4/CD3γ和Tac/CD3γ嵌合体中，该基序不依赖磷酸化而组成性激活，并导致这些嵌合体快速内化并分选至溶酶体降解。由于TCRζ链可将不完全的TCR复合物从溶酶体降解中拯救出来，并允许完全组装的TCR在细胞表面稳定表达，我们探讨了TCRζ是否有潜力掩盖CD3γ基于亮氨酸的基序这一问题。通过研究CD4/CD3γ和CD16/CD3γ嵌合体，我们发现CD16/CD3γ嵌合体与TCRζ相关。CD16/CD3γ-TCRζ复合物在细胞表面稳定表达，且自发内化率低，表明这些复合物中基于亮氨酸的基序是无活性的。相反，CD4/CD3γ嵌合体不与TCRζ相关，这些嵌合体中基于亮氨酸的基序组成性激活，导致自发内化率高且在细胞表面的表达低。因此，我们的数据表明，TCRζ通过其掩盖此类基序的潜力，使含有CD3γ基于亮氨酸基序的受体在细胞表面稳定表达。
