T-CELL RECEPTOR-ZETA ALLOWS STABLE EXPRESSION OF RECEPTORS CONTAININGTHE CD3-GAMMA LEUCINE-BASED RECEPTOR-SORTING MOTIF

The leucine-based motif in the T cell receptor (TCR) subunit CD3 gamma constitutes a strong internalization signal. In fully assembled TCR t his motif is inactive unless phosphorylated, In contrast, the motif is constitutively active in CD4/CD3 gamma and Tac/CD3 gamma chimeras ind ependently of phosphorylation and leads to rapid internalization and s orting of these chimeras to lysosomal degradation. Because the TCR zet a chain rescues incomplete TCR complexes from lysosomal degradation an d allows stable surface expression of fully assembled TCR, we addresse d the question whether TCR zeta has the potential to mask the CD3 gamm a leucine-based motif. By studying CD4/CD3 gamma and CD16/CD3 gamma ch imeras, we found that CD16/CD3 gamma chimeras associated with TCR zeta . The CD16/CD3 gamma-TCR zeta complexes were stably expressed at the c ell surface and had a low spontaneous internalization rate, indicating that the leucine-based motif in these complexes was inactive. In cont rast, the CD4/CD3 gamma chimeras did not associate with TCR zeta, and the leucine-based motif in these chimeras was constitutively active re sulting in a high spontaneous internalization rate and low expression of the chimeras at the cell surface. Thus, our data demonstrate that T CR zeta allows stable cell surface expression of receptors containing CD3 gamma leucine-based motifs by its potential to mask such motifs.