title: Transport of misfolded endoplasmic reticulum proteins to the cell surface by MHC class II molecules.
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.
authors: Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
authors: Yan
authors: Y
authors: Jiang
authors: Noriko
authors: N
authors: Arase
authors: Masako
authors: M
authors: Kohyama
authors: Kouyuki
authors: K
authors: Hirayasu
authors: Tadahiro
authors: T
authors: Suenaga
authors: Hui
authors: H
authors: Jin
authors: Maki
authors: M
authors: Matsumoto
authors: Kyoko
authors: K
authors: Shida
authors: Lewis L
authors: LL
authors: Lanier
authors: Takashi
authors: T
authors: Saito
authors: Hisashi
authors: H
authors: Arase
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D057809:HEK293 Cells; D015236:HLA-C Antigens / Q000276:immunology / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D011485:Protein Binding; D017510:Protein Folding; D021381:Protein Transport
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D001324:Autoantigens; D015236:HLA-C Antigens; C039966:HLA-C*04 antigen; D000949:Histocompatibility Antigens Class II; C045084:invariant chain