title: Refolding and reassembly of separate alpha and beta chains of class II molecules of the major histocompatibility complex leads to increased peptide-binding capacity.
abstract: Class II molecules of the major histocompatibility complex present antigenic peptides to helper T cells. These are heterodimeric glycoproteins consisting of one alpha and one beta chain. Two different alpha/beta heterodimeric conformations as well as the separate alpha and beta chains bind specific peptides. The alpha chain is thought to have one and the beta chain two intramolecular disulfide bonds. In the present study we have reduced these disulfide bonds in the murine major histocompatibility complex molecule I-Ad, which led to the release of bound peptides from all conformations and to unfolding of the separate chains. The separate alpha and beta chains could be refolded to their native structure by reoxidation of the cysteines. Refolding was accompanied by reassembly of the separated chains to the alpha/beta heterodimer. Both the separated alpha and beta chains and the alpha/beta heterodimer bound significantly higher amounts of antigenic peptide after reduction and reoxidation, as compared to the untreated protein.
authors.affiliation: Stauffer Laboratory of Physical Chemistry, Stanford University, CA 94305.
authors.forename: K
authors.initials: K
authors.lastname: Dornmair
authors.forename: H M
authors.initials: HM
authors.lastname: McConnell
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004220:Disulfides; D004591:Electrophoresis, Polyacrylamide Gel; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D010084:Oxidation-Reduction; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D004220:Disulfides; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D010455:Peptides