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Curr Opin Immunol. 2008 Feb;20(1):75-81. doi: 10.1016/j.coi.2007.12.005.

Molecular machinations of the MHC-I peptide loading complex.

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Department of Biochemistry and Molecular Biology, Bio21 Institute for Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010, Australia.


The acquisition of an optimal peptide ligand by MHC class I molecules is crucial for the generation of immunity to viruses and tumors. This process is orchestrated by a molecular machine known as the peptide loading complex (PLC) that consists of specialized and general ER-resident molecules. These proteins collaborate to ensure the loading of an optimal peptide ligand into the antigen binding cleft of class I molecules. The surprising diversity of peptides bound to MHC class I molecules and recapitulation of class I assembly in vitro have provided new insights into the molecular machinations of peptide loading. Coupled with the extraordinary polymorphism of class I molecules and their differential dependence on various components of the PLC for cell surface expression, a picture of peptide loading at the molecular level has recently emerged and will be discussed herein.

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