Recognition for degradation in the endoplasmic reticulum and lysosomes prevents the transport of single TCR beta and CD3 delta subunits of the T-cell antigen receptor to the surface of cells.
The T cell antigen receptor is a multiple subunit membrane protein made from six different polypeptide chains (alpha beta gamma delta epsilon zeta). 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 TCR beta and CD3 delta subunits in detail. After a lag period of approximately 90 min both chains were degraded by a process which did not require their transport to the medial Golgi. Degradation was inhibited at temperatures below 18 degrees but was unaffected by agents that disrupted the ER to Golgi transport. Experiments using transfected Chinese hamster ovary Lec 1 cells suggested that CD3 delta was degraded without transport to the cis-Golgi. Lysosomotropic agents had no effect on the proteolysis of the beta chain but did prevent the degradation of approximately 25% of the delta subunit. In the presence of chloroquine the delta 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 beta and delta subunits of the T cell antigen receptor; nevertheless, some of the delta chain is able to evade this process. Interestingly, there is a second check on the transport of delta to the plasma membrane, and the subunit is removed from the secretory pathway and delivered to lysosomes for degradation.
Wileman
T
T
Laboratory of Molecular Immunology, Dana Farber, Cancer Institute, Boston MA 02115.
Pettey
C
C
Terhorst
C
C
D000818:Animals; D001693:Biological Transport, Active; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006056:Golgi Apparatus / Q000276:immunology / Q000378:metabolism; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013696:Temperature; D014162:Transfection
D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta