免疫識別と応答の多様性の分子機構

• 研究課題/領域番号: 08282104
• 研究種目: 特定領域研究(A)
• 配分区分: 補助金
• 研究機関: 熊本大学 (1998-1999); 九州大学 (1996-1997)
• 研究代表者: 西村 泰治 (1998-1999) 熊本大学, 大学院・医学研究科, 教授 (10156119); 笹月 健彦 (1996-1997) 九州大学, 生体防御医学研究所, 教授 (50014121)
• 研究分担者: 吉開 泰信 名古屋大学, 医学部, 教授 (90158402) ; 武田 俊一 京都大学, 医学研究科, 教授 (60188191) ; 稲葉 カヨ 京都大学, 医学研究科, 教授 (00115792) ; 猪子 英俊 東海大学, 医学部, 教授 (10101932) ; 笠原 正典 総合研究大学院大学, 先導科学研究科, 教授 (30241318) ; 福井 宣規 九州大学, 生体防御医学研究所, 助手 (60243961) ; 西村 泰治 熊本大学, 大学院・医学研究科, 教授 (10156119) ; 菊谷 仁 大阪大学, 微生物病研究所, 教授 (80161412)
• 研究期間 (年度): 1999
• 研究課題ステータス: 完了 (1999年度)
• 配分額: 163,500千円 (直接経費: 163,500千円); 1999年度: 38,300千円 (直接経費: 38,300千円); 1998年度: 35,500千円 (直接経費: 35,500千円); 1997年度: 40,200千円 (直接経費: 40,200千円); 1996年度: 49,500千円 (直接経費: 49,500千円)
• キーワード: MHC / T細胞抗原受容体 / 樹状細胞 / 抗原提示 / γδT細胞 / HLAゲノム解析 / プロテマソーム / Toll-like receptor / T細胞 / 抗原提示細胞 / 抗原ペプチド / T細胞活性化 / T細胞分化 / MHCの進化 / HLA / CD40 / 自己免疫疾患 / NK1.1 / プロテアソーム

研究概要

MHCの構造と機能を解析して、その成果を免疫病の病因・病態の解明に資することを目的として研究を実施し、以下のような成果を得た。
1)CLIP部分をランダム配列ペプチドに置換したインバリアント鎖ライブライーを作製し、HLA-DR遺伝子と共にCOS細胞に一過性発現させ、共培養したT細胞クローンの応答を検出することにより、T細胞クローンが認識するTCRリガンドを同定するシステムを構築した(西村)。
2)未熟な樹状細胞は抗原ペプチド・MHCクラスII複合体を形成しないが、成熟刺激により速やかにこれを形成して、CD80等の共刺激分子と共に細胞表面に発現し、特異的T細胞を活性化する(稲葉)。
3)Ly49C/I^+NK1.1^+γδT細胞細胞は胸腺内でMHCクラスI分子により分化の抑制を受ける。またinvariantVg6/Vd1鎖を発現するγδT細胞細胞は、Toll-like receptor-2を介して細菌成分に直接反応する(吉開)。
4)HLA領域のマイクロサテライト多型を解析し、尋常性乾癬ではHLA-C遺伝子のテロメア側にある新規遺伝子が、またベーチェット病ではHLA-B51遺伝子そのものが疾患感受性遺伝子であることを示した(猪子)。
5)HLA領域内の全遺伝子の1/3がHLAとパラロガスな3つの領域にパラロガスなコピーをもつ。Proteasome activatorγ遺伝子標的欠損マウスでは成長遅滞がおきるが、免疫系に異常は認められない(笠原)。
6)TCRα-/-classII-/-マウス(H-2^b)由来のCD8^+T細胞も、B6マウスのAPCに対してアロ刺激に対する応答と同レベルで強く反応することより、1種類のαβTCRがclassIとclassIIの両分子に反応できる(武田)。
以上の研究により、当初の目的をほぼ達成できた。

研究成果

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