Recognition for degradation in the endoplasmic reticulum and lysosomes prevents the transport of single TCRβ and CD3δ subunits of the T-cell antigen receptor to the surface of cells

Abstract

The T cell antigen receptor is a multiple subunit membrane protein made from six different polypeptide chains (αβγδεζ) The subunits are transmembrane proteins but only receptors assembled from all six chains are transported efficiently to the plasma membrane. Partial receptors and single subunits fail to reach the Golgi apparatus. This study has used transfected fibroblasts to follow the intracellular fate of the TCRβ and CD3δ subunits in detail. After a lag period of ˜90 mm both chains were degraded by a process which did not require their transport to the medial Golgi. Degradation was inhibited at temperatures below 18° but was unaffected by agents that disrupted the ER to Golgi transport. Experiments using transfected Chinese hamster ovary Lec 1 cells suggested that CD3δ was degraded without transport to the cls-Golgi. Lysosomotropic agents had no effect on the proteolysis of the β chain but did prevent the degradation of ˜25% of the δ subunit. In the presence of chloroquine the δ subunit could be detected in lysosomes. The experiments show that proteolysis in or close to the endoplasmic reticulum plays a major role in preventing the surface expression of single βand δ subunits of the T cell antigen receptor; nevertheless, some of the δ chain is able to evade this process. Interestingly, there is a second check on the transport of δ to the plasma membrane, and the subunit is removed from the secretory pathway and delivered to lysosomes for degradation.