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 comp lex has resulted in an appreciation of the co-ordinated and multifaceted na ture of HLA class I assembly in the lumen of the endoplasmic reticulum. Thi s loading complex consists of the assembling class I heterodimer in associa tion with a number of molecular chaperones. These chaperones can be classif ied as generic to the folding of most glycoproteins in the endoplasmic reti culum or specific to the class I loading pathway. The functions of the vari ous components of the loading complex in class I molecule assembly are revi ewed. A critical component of the class I loading complex is the specialise d 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 repe rtoire selection for class I-restricted presentation in normal antigen pres enting cells. The potential implications in vaccine design and autoimmunity are discussed. (C) 2000 Elsevier Science Ltd. All rights reserved.