International Immunology, Vol. 13, No. 8, 1063-1073,
August 2001
© 2001 Japanese Society for Immunology
Distinct differences in association of MHC class I with endoplasmic reticulum proteins in wild-type, and ß2-microglobulin- and TAP-deficient cell lines
1 Tumor Immunology, Lund University, Solvegatan 21, 22362 Lund, Sweden
2 Immunology Group, Department of Pediatric Gastroenterology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK
3 Ludwig Institute for Cancer Research, Box 240, 17177 Stockholm, Sweden
4 Department of Biological Sciences, Brunel University, Uxbridge, Middlesex UB8 3PH, UK
Correspondence to: S. Li
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 ß 2 -microglobulin (ß 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 ß 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 ß 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–ß 2 m associated with calreticulin and tapasin, whereas no interaction with calnexin and BiP was observed. In the absence of ß 2 m, HC were rapidly degraded in the ER, while the ER retained HC were stabilized in the presence of ß 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.
Keywords: ß 2 -microglobulin, assembly, chaperones, MHC class I
Transmitting editor: E. Möller
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Garstka, B. Borchert, M. Al-Balushi, P. Praveen, N. Kuhl, I. Majoul, R. Duden, and S. Springer Peptide-receptive Major Histocompatibility Complex Class I Molecules Cycle between Endoplasmic Reticulum and cis-Golgi in Wild-type Lymphocytes J. Biol. Chem., October 19, 2007; 282(42): 30680 - 30690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Santos, E. C. Campbell, S. Lynch, V. Wong, A. N. Antoniou, and S. J. Powis Major Histocompatibility Complex Class I-ERp57-Tapasin Interactions within the Peptide-loading Complex J. Biol. Chem., June 15, 2007; 282(24): 17587 - 17593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Paulsson, M. Jevon, J. W. Wang, S. Li, and P. Wang The double lysine motif of tapasin is a retrieval signal for retention of unstable MHC class I molecules in the endoplasmic reticulum. J. Immunol., June 15, 2006; 176(12): 7482 - 7488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Frenkel, M. Shenkman, M. Kondratyev, and G. Z. Lederkremer Separate Roles and Different Routing of Calnexin and ERp57 in Endoplasmic Reticulum Quality Control Revealed by Interactions with Asialoglycoprotein Receptor Chains Mol. Biol. Cell, May 1, 2004; 15(5): 2133 - 2142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. PAULSSON and P. WANG Quality control of MHC class I maturation FASEB J, January 1, 2004; 18(1): 31 - 38. [Abstract] [Full Text] [PDF]
|
|