Distinct differences in association of MHC class I with endoplasmic reticulum proteins in wild-type, and β2-microglobulin- and TAP-deficient cell lines

Open Access
Publisher Website
Google Scholar
Abstract
In this study we have compared the interaction of human MHC class I molecules with IgG heavy chain (HC) binding protein (BiP), calnexin, calreticulin, tapasin and TAP in β 2 -microglobulin (β 2 m)- or TAP-deficient cells, as well as in wild-type B-LCL cells. Distinct differences between the association of HC and these endoplasmic reticulum (ER) proteins were found in the three cell lines. In the absence of β 2 m (Daudi cells), HC associated with both BiP and calnexin. A prominent portion of HC was complexed simultaneously to both chaperones, as indicated by co-precipitation with either anti-calnexin or anti-class I antisera. In the presence of β 2 m, but absence of TAP (T2 cells), HC could be co-precipitated with calnexin, whereas no detectable interaction with BiP could be demonstrated. This suggests that calnexin interacts with HC at a later stage than BiP. In B-LCL cells, HC–β 2 m associated with calreticulin and tapasin, whereas no interaction with calnexin and BiP was observed. In the absence of β 2 m, HC were rapidly degraded in the ER, while the ER retained HC were stabilized in the presence of β 2 m, even in the absence of TAP. The dissociation of class I molecules from TAP in B-LCL cells correlated with the kinetics of appearance of class I molecules on the cell surface, suggesting that TAP retains peptide-free class I molecules in the ER. Taken together, our results suggest the model that BiP and calnexin sequentially control the folding of MHC class I, before MHC class I molecules associate with the loading complex.

This publication has 46 references indexed in Scilit: