title: Conformational variants of class II MHC/peptide complexes induced by N- and C-terminal extensions of minimal peptide epitopes.
abstract: Class II MHC molecules are known to exist in conformational variants. "Floppy" and "compact" forms of murine MHC molecules, for example, are discriminated by their migration behavior on SDS/PAGE and represent empty and ligand-loaded forms. Here we show that formation of distinctly faster-migrating ligand complexes (F-forms) rather than the normal compact (C-) forms of HLA-DR1 or -DR4 results from extensions of minimal peptide epitopes (such as HA306-318 or IC106-120) by approximately 10 amino acids at either the N or the C terminus. Two similar but distinct F-forms (FI and FII) were detected, depending on the site of the extension. Both F-forms were characterized by increased surface hydrophobicity and reduced SDS-stability. Native gel separations and size exclusion chromatography indicated that the F-forms had increased hydrodynamic radii compared with the C-form and an apparent size similar to that of empty MHC molecules. The regions on the ligand overhangs responsible for the effect began at a distance of approximately 5 amino acids on either side of the epitopes, comprised 4-8 amino acids (i.e., a total overhang of 9-14), and did not have a particular sequence preference. The possible functional significance of these forms is discussed.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: O
authors.initials: O
authors.lastname: Rötzschke
authors.forename: K
authors.initials: K
authors.lastname: Falk
authors.forename: J
authors.initials: J
authors.lastname: Mack
authors.forename: J M
authors.initials: JM
authors.lastname: Lau
authors.forename: G
authors.initials: G
authors.lastname: Jung
authors.forename: J L
authors.initials: JL
authors.lastname: Strominger
mesh_terms: D017951:Antigen Presentation; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006681:HLA-D Antigens / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008024:Ligands; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D000939:Epitopes; D006681:HLA-D Antigens; D008024:Ligands; D010455:Peptides