生まれながらのペントラキシンによるFcgammaRの構造認識と機能的活性化
Jinghua Lu1, Lorraine L Marnell, Kristopher D Marjon
1Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
Nature
|November 18, 2008
まとめ
ペントラキシンは,SAPと同様に,Fcgamma受容体と結合し,免疫細胞を活性化し,抗体の機能を模倣します. この発見は,先天性免疫と適応性免疫の間の進化的つながりを明らかにし,自己免疫疾患に対する新しい治療法を提供している.
科学分野:
- 免疫学 免疫学とは
- 構造生物学 構造生物学とは
- 進化生物学の進化生物学について
背景:
- ペントラキシンは,病原体認識と補完体の活性化に関与する古代の先天性免疫媒介体です.
- 最近の発見は,ペントラキシンがFcgamma受容体 (FcgammaR) と相互作用し,白血球の機能,例えばファゴサイトーシスを活性化することを示しています.
研究 の 目的:
- ペントラキシンがFcgammaR.R.に結合する構造的メカニズムを解明する.
- この相互作用が免疫反応に及ぼす機能的影響を理解する.
主な方法:
- ヒト血清のアミロイドP成分 (SAP) とFcgammaRIIa.の複雑な構造を決定するX線結晶学.
- ペントラキシン特異性と保存された認識部位を評価するための変異および結合研究.
主要な成果:
- この構造は,FcgammaRIIaがSAPペンタマーに対角的に結合する様子を明らかにし,受容体とペントラキシンのサブユニットの特定のドメインを含む.
- ペントラキシンは,多様なFcgammaR同型特異性を表しますが,保存された認識構造を共有しています.
- 溶性ペントラキシンは,FcgammaR結合においてIgGと競合し,免疫複合体媒介のファゴシトーシスを阻害する.
結論:
- ペントラキシンには,FcgammaR経路における抗体のような機能があり,先天的および適応的免疫を橋渡ししています.
- この発見は,先天的免疫認識システムと適応的免疫認識システムの間の進化的重なりを示唆している.
- この研究は,自己免疫疾患に対する潜在的な治療的影響を有しています.
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