Abstract
Most T lymphocytes express on their surfaces an oligomeric protein complex consisting of clonotypic alpha beta polypeptides associated with invariant CD3-gamma delta epsilon and zeta 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 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 alpha and CD3 delta 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 delta proteins and TCR alpha proteins occurred prior to their association with any other TCR components and that calnexin specifically interacted with unassembled TCR alpha and CD3 delta 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 alpha glycoproteins but not with CD3 delta glycoproteins. These studies define Glc trimming and calnexin association as initial molecular events in the translation of CD3 delta and TCR alpha 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 delta and TCR alpha glycoproteins involves both glycan-dependent and glycan-independent mechanisms.
Highlights
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
Cells treated with the glucosidase inhibitor castanospermine [18] (Fig. 1, right-hand side). These results show that distinct glycoforms of CD3␦ proteins are generated in splenic T cells that reflect the differential removal of Glc residues from individual glycan chains
We evaluated the role of Glc trimming and calnexin association in the oligomerization of CD3␦ and TCR␣ proteins in splenic T lymphocytes
Summary
(Received for publication, December 11, 1995, and in revised form, February 6, 1996). 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. The role of Glc trimming and calnexin association in the oligomerization of TCR proteins within the ER is poorly understood It is unknown at which stage(s) of TCR assembly Glc residues are removed from oligosaccharide chains on nascent TCR glycoproteins in any cell type. The implications of these findings on our current knowledge of TCR assembly are discussed
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