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.