title: Recognition of open conformers of classical MHC by chaperones and monoclonal antibodies.
abstract: There is considerable evidence that the conformation and stability of class I and class II major histocompatibility complex (MHC) proteins is dependent upon high-affinity peptide ligation, but structural data for an empty MHC protein unfortunately is lacking. However, several monoclonal antibodies (mAbs) that specifically detect open MHC conformers have been characterized, and they provide insights into the changes associated with peptide loading and unloading. Here, the structural changes make the argument that certain of these open conformer-specific mAbs recognize analogous MHC segments as the molecular chaperones tapasin and DM. MHC residues located in regions flanking the peptide-terminal anchoring pockets have been implicated in both chaperone and monoclonal antibody binding. Indeed, we propose these regions serve as peptide-binding hinges that are uniquely accessible in open MHC.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA. hansen@immunology.wustl.edu
authors.forename: Ted H
authors.initials: TH
authors.lastname: Hansen
authors.forename: Lonnie
authors.initials: L
authors.lastname: Lybarger
authors.forename: Lawrence
authors.initials: L
authors.lastname: Yu
authors.forename: Vesselin
authors.initials: V
authors.lastname: Mitaksov
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D017920:Antiporters / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000276:immunology*; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary
chemical_list: D000911:Antibodies, Monoclonal; D017920:Antiporters; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; C107762:tapasin