Class I MHC molecules: assembly and antigen presentation

Several years ago, the only factor known to be necessary for the assembly a nd surface expression of class I MHC was beta(2)m; even for beta(2)m, it wa s unclear at what point in class I maturation its role was played. Recent e xperiments that employed attachment of an endoplasmic reticulum (ER) retent ion signal to beta(2)m have shown that the point of time at which beta(2)m is required is while the class I heavy chain is in the ER. Later associatio n between beta(2)m and class I is not vital in order for properly folded cl ass I to be expressed at the cell surface. After crystallization of the fir st class I MHC molecule, it was realized that not only is antigen presented by class I, but that antigen is presented in the form of a peptide that st abilizes the class I structure and allows its transit to the cell surface. Class I allelic differences influence interactions with both peptide and be ta(2)m, with likely consequences for the ability of the class I heavy chain s to present antigen through alternative pathways. Furthermore, it is now a lso clear that formation of appropriate disulfide bonds in the class I heav y chain is needed before class I can bind peptide antigen securely, a proce ss that may be assisted by an ER chaperone. Many different proteins that ar e resident in the ER, such as calnexin, transporter associated with antigen processing (TAP), calreticulin, and tapasin, have been found to be integra l to class I assembly TAP, tapasin, and calreticulin bind preferentially to the open form of class I, which can be distinguished with the use of a mon oclonal antibody specific for this form. Calreticulin and calnexin contrast in their interactions with class I, despite other similarities between the se two chaperones. Overall, class I MHC assembly is now understood to invol ve the interplay of multiple intra- and intermolecular events in a defined chronological order which ensure continual reporting of cellular contents t o cytotoxic T lymphocytes.