Structural basis for immune evasion mechanism of HIV peptide mutations.

2012 Fiscal Year Final Research Report

• Project/Area Number: 22370043
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Hokkaido University
• Principal Investigator: MAENAKA Katsumi 北海道大学, 大学院・薬学研究院, 教授 (10322752)
• Project Period (FY): 2010 – 2012
• Keywords: HIV / 細胞表面受容体 / 蛋白質 / 蛋白質間相互作用 / 表面プラズモ ン共鳴 / NMR 解析 / X 線結晶構造解析 / 免疫制御

Research Abstract

MHC recognizing receptors expressed on natural killer cells and cytotoxic T cells, KIRs and LILRs, have a pivotal role on regulation of virus infection. The mutation of a HIV-derived peptide on MHC molecule disrupt T cell function and also inhibit NK function by increasing the binding activity of an inhibitory KIR. Here we successfully determined the structure of a LILR-MHC complex at low resolution, revealing that this complex structure is similar to the previously reported LILR-MHC complexes, LILR recognize the site far from the peptide-binding region and thus the HIV peptide mutations do not likely affect the LILR binding, supported by our binding study. On the other hand, we also determined the crystal structure of the MHC class I molecule displaying the HIV mutant peptide, which increased the KIR binding, revealing the molecular mechanism for the change of KIR binding activity.

Research Products

• [Journal Article] Distinct HIV-1 Escape Patterns Selected by CTLs with Identical Epitope Specificity (2013)
  • Author(s): Yagita Y, Kuse N, Kuroki K, Gatanaga H, Carlson J.M, Chikata T, Brumme Z.L., Murakoshi H, Akahoshi T, Pfeifer N, Mallal S, John M, Ose T, Matsubara H, Kanda R, Fukunaga Y, Honda K, Kawashima Y, Ariumi Y, Oka S, Maenaka K, Takiguchi M
  • Journal Title: J Virol Volume: 87(4) Pages: 2253-63
  • Peer Reviewed
• [Journal Article] HLA-B27 Homodimers and Free H Chains Are Stronger Ligands for Leukocyte Ig-like Receptor B_2 than Classical HLA Class I. (2012)
  • Author(s): Giles J, Shaw J, Piper C, Wong-Baeza I, McHugh K, Ridley A, Li D, Lenart I, Antoniou AN, Digleria K, Kuroki K, Maenaka K , Bowness P, Kollnberger S
  • Journal Title: J Immunol Volume: 188(12) Pages: 6184-93
  • Peer Reviewed
• [Journal Article] InvolvementofanNKG2DLigandH60c in Epidermal Dendritic T Cell-Mediated Wound Repair (2012)
  • Author(s): Yoshida S, Mohamed RH, Kajikawa M, Koizumi J, Tanaka M, Fugo K, Otsuka N, Maenaka K , Yagita H, Chiba H, Kasahara M
  • Journal Title: J Immunol Volume: 188(8) Pages: 3972-9
  • Peer Reviewed
• [Journal Article] Analysis of receptor-ligand interactions by surface plasmon resonance (2011)
  • Author(s): Kuroki K, Maenaka K
  • Journal Title: Methods Mol.Biol Volume: 748 Pages: 83-106
  • Peer Reviewed
• [Journal Article] Long-term control of HIV-1 in hemophiliacs carryin slow-progressing allele HLA-B*5101 (2010)
  • Author(s): Kawashima Y, Kuse N, Gatanaga H, Naruto T, Fujiwara M, Dohki S, Akahoshi T, Maenaka K , Goulder P, Oka S, Takiguchi M
  • Journal Title: J Virol Volume: 84 Pages: 7151-60
  • Peer Reviewed
• [Presentation] Structural basis for immune regulation of cell surface receptors in HIV infection (2012)
  • Author(s): Kimiko Kuroki, Haruki Matsubara, Yoichi Watanabe, Yuko Fukunaga, Ryo Kanda, Jun Kamishikiryo, Hathairat Thananchai, Tariro Makadzange, Tao Dong, Sarah Rowland-Jones, Toyoyuki Ose, and Katsumi Maenaka
  • Organizer: The 13th Kumamoto AIDS Seminar
  • Place of Presentation: Aso Resort Grandvrio Hotel (Kumamoto)
  • Year and Date: 2012-10-25
• [Presentation] ヒトKiller cellIg-like receptor群のNK細胞アロ反応性の構造基盤 (2012)
  • Author(s): 前仲勝実
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: さっぽろ芸文館(札幌)
  • Year and Date: 2012-09-20
• [Presentation] 機能および構造解析に向けた細胞表面蛋白質の調製法 (2012)
  • Author(s): 福原秀雄、橋口隆生、黒木喜美子、尾瀬農之、前仲勝実
  • Organizer: 日本蛋白質科学会・ワークショップ
  • Place of Presentation: 名古屋国際会議場(愛知)
  • Year and Date: 2012-06-20
• [Presentation] 表面タンパク質の不安定な複合体の分子解析 (2011)
  • Author(s): 前仲勝実
  • Organizer: 日本蛋白質科学会・ワークショップ
  • Place of Presentation: ホテル阪急エキスポパーク(大阪)
  • Year and Date: 2011-06-09
• [Remarks]
  • URL: http://convallaria.pharm.hokudai.ac.jp/bunshi/