The molecular chaperone calnexin is expressed on the surface of immature thymocytes in association with clonotype-independent CD3 complexes.
Immature thymocytes express clonotype-independent CD3 complexes that, when engaged by anti-CD3 antibodies, can signal CD4-CD8- thymocytes to differentiate into CD4+CD8+ cells. Clonotype-independent CD3 complexes consist of CD3 components associated with an unknown 90 kDa surface protein. We now report the surprising finding that this 90 kDa surface protein is the molecular chaperone calnexin, an integral membrane protein previously thought to reside only in the endoplasmic reticulum (ER). We found that calnexin-CD3 complexes escaping to the cell surface utilize interchain associations distinct from those utilized by calnexin-CD3 complexes remaining within the ER. Specifically, we demonstrate that carbohydrate-mediated luminal domain interactions that are necessary for formation of most internal calnexin-CD3 complexes destined to be expressed on the cell surface, and we provide evidence that cytoplasmic domain interactions between calnexin and CD3 epsilon chains mask calnexin's ER retention signal, permitting calnexin and associated proteins to escape ER retention. Thus, the present study demonstrates that partial T cell antigen receptor complexes can escape the ER of immature thymocytes in association with their molecular chaperone to be expressed at low levels on the cell surface where they may function as a signaling complex to regulate thymocyte maturation.
Wiest
D L
DL
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Burgess
W H
WH
McKean
D
D
Kearse
K P
KP
Singer
A
A
D000595:Amino Acid Sequence; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry; D037281:Calnexin; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D011485:Protein Binding; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
D017252:CD3 Complex; D002135:Calcium-Binding Proteins; D018832:Molecular Chaperones; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D037281:Calnexin