Calnexin Associates Exclusively with Individual CD3 and T Cell Antigen Receptor (TCR) Proteins Containing Incompletely Trimmed Glycans That Are Not Assembled into Multisubunit TCR Complexes

Jeroen E. M. van Leeuwen, Kelly P. Kearse
1996 Journal of Biological Chemistry  
Most T lymphocytes express on their surfaces an oligomeric protein complex consisting of clonotypic ␣␤ polypeptides associated with invariant CD3-␥␦⑀ and chains, designated the T cell antigen receptor (TCR) complex. Assembly and intracellular transport of nascent TCR proteins is believed to be assisted by their interaction with the molecular chaperone calnexin, which for certain molecules functions as a lectin for monoglucosylated glycans. However, as most of our knowledge about calnexin-TCR
more » ... out calnexin-TCR protein associations has been obtained under conditions of limited TCR assembly, the role of calnexin in the formation of nascent TCR complexes is unclear. Here, we studied the role of glucose (Glc) trimming and calnexin association in the oligomerization of TCR␣ and CD3␦ glycoproteins in murine splenic T lymphocytes, a model cell type for efficient assembly of complete TCR complexes. We show that removal of Glc residues from both CD3␦ proteins and TCR␣ proteins occurred prior to their association with any other TCR components and that calnexin specifically interacted with unassembled TCR␣ and CD3␦ proteins containing incompletely trimmed oligosaccharides. Interestingly, we found that removal of Glc residues from glycan chains was necessary for efficient association of calnexin with TCR␣ glycoproteins but not with CD3␦ glycoproteins. These studies define Glc trimming and calnexin association as initial molecular events in the translation of CD3␦ and TCR␣ proteins, occurring coincident with or immediately after their translocation into the endoplasmic reticulum and preceding the ordered pairing of TCR chains. In addition, these data document that calnexin assembly with CD3␦ and TCR␣ glycoproteins involves both glycan-dependent and glycan-independent mechanisms. Assembly of the T cell antigen receptor (TCR) 1 complex occurs within the endoplasmic reticulum (ER) and proceeds in a highly ordered manner by: (i) formation of noncovalently associated pairs of ␦⑀ and ␥⑀ proteins, (ii) association of individual clonotypic ␣, ␤ polypeptides with ␦⑀ and ␥⑀ pairs to form intermediate ␣␦⑀ and ␤␥⑀ protein complexes, (iii) rapid pairing of
doi:10.1074/jbc.271.16.9660 pmid:8621641 fatcat:pywemrrwd5cqtebxncpiqt32tq