title: Single-molecule motions of MHC class II rely on bound peptides.
abstract: The major histocompatibility complex (MHC) class II protein can bind peptides of different lengths in the region outside the peptide-binding groove. Peptide-flanking residues (PFRs) contribute to the binding affinity of the peptide for MHC and change the immunogenicity of the peptide/MHC complex with regard to T cell receptor (TCR). The mechanisms underlying these phenomena are currently unknown. The molecular flexibility of the peptide/MHC complex may be an important determinant of the structures recognized by certain T cells. We used single-molecule x-ray analysis (diffracted x-ray tracking (DXT)) and fluorescence anisotropy to investigate these mechanisms. DXT enabled us to monitor the real-time Brownian motion of the peptide/MHC complex and revealed that peptides without PFRs undergo larger rotational motions than peptides with PFRs. Fluorescence anisotropy further revealed that peptides without PFRs exhibit slightly larger motions on the nanosecond timescale. These results demonstrate that peptides without PFRs undergo dynamic motions in the groove of MHC and consequently are able to assume diverse structures that can be recognized by T cells.
authors.affiliation: CREST Sasaki Team, Japan Science and Technology Agency, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan; Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan. Electronic address: kozonoh@rs.noda.tus.ac.jp.
authors.forename: Haruo
authors.initials: H
authors.lastname: Kozono
authors.affiliation: Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
authors.forename: Yufuku
authors.initials: Y
authors.lastname: Matsushita
authors.affiliation: CREST Sasaki Team, Japan Science and Technology Agency, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan; Graduate School for Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ogawa
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kozono
authors.affiliation: Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyabe
authors.affiliation: CREST Sasaki Team, Japan Science and Technology Agency, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan; Japan Synchrotron Radiation Research Institute, Hyogo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sekiguchi
authors.affiliation: CREST Sasaki Team, Japan Science and Technology Agency, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan; Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Ichiyanagi
authors.affiliation: Computational Biology Research Core, Quantitative Biology Center, RIKEN, Hyogo, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Okimoto
authors.affiliation: Computational Biology Research Core, Quantitative Biology Center, RIKEN, Hyogo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Taiji
authors.affiliation: CREST Sasaki Team, Japan Science and Technology Agency, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan; Centre International de Recherche en Infectiologie, INSERM U1111, Lyon, France.
authors.forename: Osami
authors.initials: O
authors.lastname: Kanagawa
authors.affiliation: CREST Sasaki Team, Japan Science and Technology Agency, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan; Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan. Electronic address: ycsasaki@k.u-tokyo.ac.jp.
authors.forename: Yuji C
authors.initials: YC
authors.lastname: Sasaki
mesh_terms: D000595:Amino Acid Sequence; D005454:Fluorescence Polarization; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009038:Motion; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D014961:X-Ray Diffraction
chemical_list: D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments