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LRRを用いた抗原認識システムの開発

Research Project

Project/Area Number 19659120
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionHokkaido University

Principal Investigator

笠原 正典  北海道大学, 大学院・医学研究科, 教授 (30241318)

Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywords抗体 / 抗原認識 / leucine-rich repeat / VLR / 無顎類 / 結晶構造
Research Abstract

無顎類(メクラウナギ,ヤツメウナギ)の抗原レセプターであるvariable lymphocyte receptor (VLR) は,免疫グロブリンやT細胞レセプターと異なり,leucine-rich repeats (LRR) をモジュールとして遺伝子再構成を行うことにより,10^<14>にも及ぶ多様性を作り出し,高い親和性と特異性をもって抗原に結合する.この事実は,無顎類には有顎類のそれとは原理的に異なる抗原特異的な生体識別機構が存在することを示唆しており,興味深い.本研究では,VLRが抗原を特異的に認識することに着目して、VLRのLRRモジュールを利用して,抗体の代用となる抗原認識試薬の開発を目指すことを最終的な目的としている.本年度は,飼育可能で入手しやすいヤツメウナギのVLRシステムの詳細な解析を行った.その結果,ヤツメウナギには従来から知られていたVLRA,VLRB遺伝子のほかに,VLRCと命名した第3のVLR遺伝子が存在することを見出した.VLRC遺伝子は,1) VLRB遺伝子の発現を誘導する抗原刺激を与えても発現が誘導されない,2) LRRCT領域における多様性が乏しい,などの特徴を有している.さらに,種々のヒト細胞株,アロ血球,糖鎖抗原で免疫したヤツメウナギから白血球を分離し,cDNAを作成し,ファージディスプレイライブラリーを作成した.現在,パンニングにより,免疫源と特異的に反応するファージクローンを探索している段階である.

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (14 results)

All 2008 2007

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] The amphioxus genome ilium inates vertebrate origins and cephalochordate biology.2008

    • Author(s)
      Holland, L.Z.
    • Journal Title

      Genome Res.

      Volume: 18 Pages: 1100-1111

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two types of antigen receptor systems in vertebrates.2008

    • Author(s)
      Kasahara, M.
    • Journal Title

      Zoolog. Sci.

      Volume: 25 Pages: 969-975

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of a chaperone complex that contributes to the assembly of yeast 20S proteasomes.2008

    • Author(s)
      Yashiroda, H.
    • Journal Title

      Nat. Struct. Mol. Biol. 15

      Pages: 228-236

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two novel NKG2D ligands of the mouse H60 family with differential expression patterns and binding affinities to NKG2D.2008

    • Author(s)
      Takada, A.
    • Journal Title

      J. Immunol. 180

      Pages: 1678-1685

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rat CD4+/CD8+macrophages kill tumor cells through an NKG2D- and granzyme/perforin-dependent mechani2008

    • Author(s)
      Baba, T.
    • Journal Title

      J. Immunol. 180

      Pages: 2999-3006

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evidence for the involvement of testicular protein CRISP2 in mouse sperm-egg fusion.2007

    • Author(s)
      Busso, D.
    • Journal Title

      Biol. Reprod. 76

      Pages: 701-708

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two variable lymphocyte receptor genes of the inshore hagfish are located far apart on the same chromosome.2007

    • Author(s)
      Kasamatsu, J.
    • Journal Title

      Immunogenetics 59

      Pages: 329-331

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced production of p24 Gag protein in HIV-1-infected rat cells fused with uninfected human cells.2007

    • Author(s)
      Chen, J.
    • Journal Title

      Exp. Mol. Pathol. 83

      Pages: 125-130

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The 2R hypothesis: An update.2007

    • Author(s)
      Kasahara, M.
    • Journal Title

      Curr. Opin. Immunol. 19

      Pages: 547-552

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A degenerate ParaHox gene cluster in a degenerate vertebrate.2007

    • Author(s)
      Furlong. R. F.
    • Journal Title

      Mol. Biol. Evol. 24

      Pages: 2681-2686

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Structural and genetic analysis of the variable lymphocyte receptor family.2008

    • Author(s)
      Kasamatsu, J.
    • Organizer
      日本分子生物学会第8回春季シンポジウム
    • Place of Presentation
      札幌
    • Related Report
      2008 Annual Research Report
  • [Presentation] Structural and genetic analysis of variable lymphocyte receptors2008

    • Author(s)
      Kasamatsu, J.
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] Two novel NKG2D ligands of the mouse H60 family with differential expression patterns and binding affinities2007

    • Author(s)
      Yoshida, S.
    • Organizer
      第66回日本癌学会学術集会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 特許権2008

    • Inventor(s)
      笠原正典, 他
    • Industrial Property Rights Holder
      北海道大学
    • Industrial Property Number
      2008-305003
    • Filing Date
      2008-11-28
    • Related Report
      2008 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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