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 c omplexes consist of CD3 components associated with an unknown 90 kDa s urface protein, We now report the surprising finding that this 90 kDa surface protein is the molecular chaperone calnexin, an integral membr ane protein previously thought to reside only in the endoplasmic retic ulum (ER), We found that calnexin-CD3 complexes escaping to the cell s urface utilize interchain associations distinct from those utilized by calnexin-CD3 complexes remaining within the ER, Specifically, we demo nstrate that carbohydrate-mediated luminal domain interactions that ar e necessary for formation of most internal calnexin-CD3 complexes are not required for formation of calnexin-CD3 complexes destined to be ex pressed on the cell surface, and we provide evidence that cytoplasmic domain interactions between calnexin and CD3 epsilon chains mask calne xin's ER retention signal, permitting calnexin and associated proteins to escape ER retention, Thus, the present study demonstrates that par tial T cell antigen receptor complexes can escape the ER of immature t hymocytes in association with their molecular chaperone to be expresse d at low levels on the cell surface where they may function as a signa ling complex to regulate thymocyte maturation.