The nature of the MHC class I peptide loading complex

Peptide binding to major histocompatibility complex (MHC) class I molecules occurs in the endoplasmic reticulum (ER). Efficient peptide binding requir es a number of components in addition to the MHC class I-beta(2) microglobu lin dimer (beta(2)m). These include the two subunits of the transporter ass ociated with antigen presentation (TAP1 and TAP2), which are essential for introducing peptides into the ER from the cytosol, and tapasin, an MHC-enco ded membrane protein. Prior to peptide binding, MHC class I-beta(2)m dimers form part of a large multisubunit ER complex which includes TAP and tapasi n. In addition to these specialized components two soluble 'house-keeping' proteins, the chaperone calreticulin and the thiol oxidoreductase ERp57, ar e also components of this complex. Our current understanding of the nature and function of the MHC class I peptide loading complex is the topic of thi s review.