The peptide-loading complex and ligand selection during the assembly of HLA class I molecules.
The identification and characterisation of the class I peptide loading complex has resulted in an appreciation of the co-ordinated and multifaceted nature of HLA class I assembly in the lumen of the endoplasmic reticulum. This loading complex consists of the assembling class I heterodimer in association with a number of molecular chaperones. These chaperones can be classified as generic to the folding of most glycoproteins in the endoplasmic reticulum or specific to the class I loading pathway. The functions of the various components of the loading complex in class I molecule assembly are reviewed. A critical component of the class I loading complex is the specialised chaperone tapasin. The role of tapasin in the stabilisation and retention of empty or suboptimally loaded class I molecules and the facilitation of the loading of these molecules with more appropriate ligands is discussed. As such, it is proposed that tapasin is a major determinant of peptide repertoire selection for class I-restricted presentation in normal antigen presenting cells. The potential implications in vaccine design and autoimmunity are discussed.
Purcell
A W
AW
The Department of Microbiology and Immunology, University of Melbourne, 3052, Victoria, Parkville, Australia. a.purcell@microbiology.unimelb.edu.au
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D017920:Antiporters / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D008024:Ligands; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D011110:Polymorphism, Genetic; D013329:Structure-Activity Relationship
D017920:Antiporters; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D008024:Ligands; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D010455:Peptides; C107762:tapasin