期刊
INTERNATIONAL IMMUNOLOGY
卷 25, 期 4, 页码 235-246出版社
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxs155
关键词
antigen presentation; B cell activation; MHC class II; misfolded protein
类别
资金
- Ministry of Education, Science and Culture, Japan
- National Institutes of Health [AI068129]
- Grants-in-Aid for Scientific Research [24659223, 24115005, 23790385, 23790504] Funding Source: KAKEN
Misfolded endogenous ER proteins can be presented intact by MHC class II and stimulate B cells.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.
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