Peptide exchange in MHC molecules.
Major histocompatibility complex (MHC)-encoded glycoproteins bind peptide antigens through non-covalent interactions to generate complexes that are displayed on the surface of antigen-presenting cells (APC) for recognition by T cells. Peptide-binding site occupancy is necessary for stable assembly of newly synthesized MHC proteins and export from the endoplasmic reticulum (ER). The MHC class II antigen-processing pathway provides a mechanism for presentation of peptides generated in the endosomal pathway of APC. The chaperone protein, invariant chain, includes a surrogate peptide that stabilizes newly synthesized class II molecules during transport to endosomal compartments. The invariant chain-derived peptide must be replaced through a peptide exchange reaction that is promoted by acidic pH and the MHC-encoded co-factor HLA-DM. Peptide exchange reactions are not required for presentation of antigens by MHC class I molecules because they bind antigens during initial assembly in the ER. However, exchange reactions may play an important role in editing the repertoire of peptides presented by both class II and class I molecules, thus influencing the specificity of immunity and tolerance.
Jensen
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Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA. pjensen@bimcore.emory.edu
Weber
D A
DA
Thayer
W P
WP
Westerman
L E
LE
Dao
C T
CT
D000818:Animals; D017951:Antigen Presentation; D015551:Autoimmunity; D006681:HLA-D Antigens / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*
C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides