Assembly of MHC class I peptide complexes from the perspective of disulfide bond formation.
Assembly of functional major histocompatibility complex (MHC) class I peptide complexes within the endoplasmic reticulum is critically important for the development of an adaptive immune response. The highly regulated loading of peptides onto MHC class I molecules is controlled by a multi-component chaperone system called the MHC class I peptide loading complex. The recent identification of the thioredoxin family member ERp57 as a component of the loading complex led to an interesting question: Why is there a thiol-disulfide oxidoreductase inside a complex dedicated to inserting peptides into a receptor binding site? Most recently, specific ERp57-mediated disulfide bond rearrangements have been identified inside the loading complex. What these biochemical events mean for the peptide loading process remains a matter of conjecture. While several important questions wait to be answered, this review intends to summarize our current view of the oxidative folding of MHC class I molecules and addresses the question of how the receptor ligand interaction might be regulated by thiol-based redox reactions.
German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. t.dick@dkfz.de.
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D000818:Animals; D017951:Antigen Presentation; D003545:Cysteine / Q000378:metabolism*; D003553:Cystine / Q000096:biosynthesis*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D013438:Sulfhydryl Compounds; D003553:Cystine; D003545:Cysteine