Transport of misfolded endoplasmic reticulum proteins to the cell surface by MHC class II molecules
Open Access
- 18 January 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in International Immunology
- Vol. 25 (4), 235-246
- https://doi.org/10.1093/intimm/dxs155
Abstract
Nascent MHC class II molecules are associated with the invariant chain and are transported to the endolysosomal pathway, where MHC class II molecules acquire peptide antigens. On the other hand, misfolded endoplasmic reticulum (ER) proteins are generally degraded in the cells and are neither expressed on the cell surface nor secreted. Here, we found that MHC class II molecules associate with some misfolded ER proteins via the peptide-binding groove in competition with invariant chain. The misfolded proteins associated with MHC class II molecules are transported intact to the cell surface without processing to peptides. Furthermore, these complexes efficiently stimulate antigen-specific B cells. These findings reveal that MHC class II molecules function as a chaperone for the cell surface expression of misfolded ER proteins. In addition, we suggest that MHC class II molecules present not only peptides but also intact host-cell-derived proteins on the cell surface. These findings provide new insights into the function of MHC class II molecules.Keywords
This publication has 33 references indexed in Scilit:
- Towards a systems understanding of MHC class I and MHC class II antigen presentationNature Reviews Immunology, 2011
- PILRα Is a Herpes Simplex Virus-1 Entry Coreceptor That Associates with Glycoprotein BCell, 2008
- Open conformers: the hidden face of MHC-I moleculesTrends in Immunology, 2007
- Extrafollicular Activation of Lymph Node B Cells by Antigen-Bearing Dendritic CellsScience, 2006
- HLA‐C heavy chains free of ß2‐microglobulin: distribution in normal tissues and neoplastic lesions of non‐lymphoid origin and interferon‐γ responsivenessTissue Antigens, 1997
- The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3Nature, 1995
- Production of soluble MHC class II proteins with covalently bound single peptidesNature, 1994
- Assembly, Transport, and Function of MHC Class II MoleculesAnnual Review of Immunology, 1994
- Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptideNature, 1994
- Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in sizeNature, 1992