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.