The Role of Calnexin and Calreticulin in MHC Class I Assembly

Abstract

Assembly of Major Histocompatibility Complex (MHC) class I heavy chain (HC) with $β$2-microglobulin ($β$2m) and subsequent acquisition of optimal peptides is necessary for class 1 antigen presentation to cytotoxic T cells (CTLs). Calnexin and calreticulin are two major chaperones involved in the assembly of class I. Recent findings suggest calnexin is important in early stages of class I assembly where it recruits Erp57 to facilitate disulphide bond formation in class I HC and protects class I HC from degradation prior to their assembly with $β$2m. In addition, assembly of class I HC with $β$2m is reduced in the absence of calnexin suggesting a direct involvement of calnexin in the assembly of HC with $β$2m. Calreticulin, on the other hand, is involved in the later stages of class I assembly. Studies of a calreticulin-deficient cell line has demonstrated its critical role in the peptide loading of class I molecules.