新しい細胞間粘着分子ICAM-Rのクローン化と特徴づけ
R Vazeux1, P A Hoffman, J K Tomita
1ICOS Corporation, Bothell, Washington 98021.
Nature
|December 3, 1992
まとめ
研究者は,新しい細胞間粘着分子であるICAM-Rを特定しました. ICAM-1とICAM-2に関連したこの分子は,内皮細胞とは異なる白血球のLFA-1に結合します.
科学分野:
- 免疫学 免疫学とは
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
背景:
- ICAM-1とICAM-2のような細胞間粘着分子 (ICAM) とβ2インテグリン (白血球インテグリン) は,白血球と内皮細胞の粘着に不可欠であり,免疫機能に不可欠です.
- ICAM-1およびICAM-2に対する抗体を用いた白血球機能関連抗原LFA-1-依存付着の完全な阻害は,以前に特定されたICAM-3のような他のLFA-1リガンドの存在を示唆しています.
研究 の 目的:
- ICAM-R.と指定されたICAMファミリーの新しいメンバーを分子的にクローンし,特徴づけること.
- ICAM-RとICAM-1およびICAM-2との構造的,機能的な関係を調査する.
- ICAM-R.の発現パターンとリガンド結合特性を決定する.
主な方法:
- ICAM-R.をコードする補完DNA (cDNA) の分子クローニング
- ICAM-Rタンパク質配列とドメイン構造の分析.
- ICAM-R.の成熟した細胞表面形態の分子量 (M(r)) の決定.
- タンパク質配列の同一性をICAM-1とICAM-2と比較する.
- 休息状態と活性状態の異なる細胞タイプ (白血球と内皮細胞) のICAM-R発現の評価.
- ICAM-RがCD11a/LFA-1のリガンドであることを確認するための機能分析.
主要な成果:
- 新しいICAMファミリーのメンバーであるICAM-Rが分子的にクローンされました. そのcDNAは1,781塩基対の長さで,細胞外免疫グロブリンファミリーの型ドメインが5つあるタンパク質をコードする.
- 成熟したICAM-Rタンパク質は,細胞型に特異な分子量116K~140Kを示しています.
- ICAM-RとICAM-1のタンパク質配列の同一性は48%,ICAM-2は31%で,ドメインの違いがある.
- ICAM-Rは,すべての系統の静止白血球に高度に発現するが,静止またはサイトカインで活性化された内皮細胞には発現しないので,その発現はICAM-1およびICAM-2と異なる.
- ICAM-Rは,ICAM-1およびICAM-2と同様に,β2-インテグリンCD11a/LFA-1のリガンドとして機能します.
結論:
- ICAM-Rは,独特の構造と表現の特徴を持つICAMファミリーの新たに特定されたメンバーを表しています.
- 白血球におけるICAM-Rのユニークな発現パターンは,白血球の結合と免疫反応における特定の役割を示唆しています.
- ICAM-RのLFA-1を結合する能力は,さらに白血球の密輸と免疫システム内の相互作用に関与することを示唆しています.
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