title: Control of MHC class I traffic from the endoplasmic reticulum by cellular chaperones and viral anti-chaperones.
abstract: MHC class I molecules assemble with peptides in the endoplasmic reticulum (ER). To ensure that only peptide-loaded MHC molecules leave the ER, empty molecules are retained by ER-resident chaperones, most notably the MHC-specific tapasin. ER exit of class I MHC is also controlled by viruses, but for the opposite purpose of preventing peptide presentation to T cells. Interestingly, some viral proteins are able to retain MHC class I molecules in the ER despite being transported. By contrast, other viral proteins exit the ER only upon binding to class I MHC, thereby rerouting newly synthesized class I molecules to intracellular sites of proteolysis. Thus, immune escape can be achieved by reversing, inhibiting or redirecting the chaperone-assisted MHC class I folding, assembly and intracellular transport.
authors.affiliation: R.W. Johnson Pharmaceutical Research Institute, 3210 Merryfield Row, San Diego, CA 92121, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gruhler
authors.forename: K
authors.initials: K
authors.lastname: Früh
mesh_terms: D017456:Adenovirus Early Proteins / Q000378:metabolism; D000818:Animals; D017920:Antiporters / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008954:Models, Biological; D018832:Molecular Chaperones; D010455:Peptides / Q000378:metabolism*; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D014780:Viruses / Q000378:metabolism
chemical_list: D017456:Adenovirus Early Proteins; D017920:Antiporters; D002352:Carrier Proteins; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D010455:Peptides; D016601:RNA-Binding Proteins; C082590:UL4 protein, Human cytomegalovirus; C074546:US11 protein, herpesvirus; C118670:US2 protein, Varicellovirus; C095111:US3 protein, cytomegalovirus; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C104832:gp34 protein, cytomegalovirus; C104783:m152 protein, cytomegalovirus; C107762:tapasin