Tapasin and other chaperones: models of the MHC class I loading complex.
MHC (major histocompatibility complex) class I molecules bind intracellular virus-derived peptides in the endoplasmic reticulum (ER) and present them at the cell surface to cytotoxic T lymphocytes. Peptide-free class I molecules at the cell surface, however, could lead to aberrant T cell killing. Therefore, cells ensure that class I molecules bind high-affinity ligand peptides in the ER, and restrict the export of empty class I molecules to the Golgi apparatus. For both of these safeguard mechanisms, the MHC class I loading complex (which consists of the peptide transporter TAP, the chaperones tapasin and calreticulin, and the protein disulfide isomerase ERp57) plays a central role. This article reviews the actions of accessory proteins in the biogenesis of class I molecules, specifically the functions of the loading complex in high-affinity peptide binding and localization of class I molecules, and the known connections between these two regulatory mechanisms. It introduces new models for the mode of action of tapasin, the role of the class I loading complex in peptide editing, and the intracellular localization of class I molecules.
Wright
Cynthia Anne
CA
Biochemistry and Cell Biology, International University Bremen, D-28759 Bremen, Germany.
Kozik
Patrycja
P
Zacharias
Martin
M
Springer
Sebastian
S
D000818:Animals; D017920:Antiporters / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D006680:HLA Antigens / Q000378:metabolism / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D021381:Protein Transport / Q000502:physiology
D017920:Antiporters; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; C107762:tapasin