Transport of misfolded endoplasmic reticulum proteins to the cell surface by MHC class II molecules

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 express...

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Bibliographic Details
Published in:International immunology 2013-04, Vol.25 (4), p.235-246
Main Authors: Jiang, Yan, Arase, Noriko, Kohyama, Masako, Hirayasu, Kouyuki, Suenaga, Tadahiro, Jin, Hui, Matsumoto, Maki, Shida, Kyoko, Lanier, Lewis L, Saito, Takashi, Arase, Hisashi
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation
Antigens, Differentiation, B-Lymphocyte - metabolism
Autoantigens - immunology
Autoantigens - metabolism
B-Lymphocytes - immunology
Cell Membrane - metabolism
Cell surface
CHO Cells
Cricetinae
Endoplasmic reticulum
Endoplasmic Reticulum - metabolism
HEK293 Cells
Histocompatibility Antigens Class II - metabolism
HLA-C Antigens - immunology
HLA-C Antigens - metabolism
Humans
Lymphocyte Activation
Lymphocytes B
Major histocompatibility complex
Mice
Protein Binding
Protein Folding
Protein Transport
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Summary: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.
ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/dxs155