title: Structural and functional mosaic nature of MHC class I molecules in their peptide-free form.
abstract: Despite well-organized peptide-loading mechanisms within the endoplasmic reticulum, major histocompatibility complex class I (MHC-I) molecules can be displayed on cell surfaces in peptide-free forms. Although these empty MHC-I (eMHC-I) molecules are presumably involved in physiological and pathological processes, little is known about their structures and functions due to their instability. Using bacterially expressed HLA-Cw*07:02 heavy chain and β2 microglobulin molecules, we successfully established an in vitro refolding method to prepare eMHC-I molecules in sufficient quantities for detailed structural analyses. NMR spectroscopy in conjunction with subunit-specific ¹⁵N-labeling techniques revealed that the peptide-binding domains and the adjacent regions were unstructured in the peptide-free form, while the remaining regions maintained their structural integrity. Consistent with our spectroscopic data, the eMHC-I complex could interact with leukocyte Ig-like receptor B1, but not with killer cell Ig-like receptor 2DL3. Thus, eMHC-I molecules have a mosaic nature in terms of their three-dimensional structure and binding to immunologically relevant molecules.
authors.affiliation: Graduate School and Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kurimoto
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kuroki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Maho
authors.initials: M
authors.lastname: Yagi-Utsumi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Igaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iguchi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
mesh_terms: D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015236:HLA-C Antigens / Q000737:chemistry / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D013329:Structure-Activity Relationship; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D001613:beta 2-Microglobulin