1型糖尿病患者の独特の二重受容体発現リンパ球に存在する公開BCRは,強力なT細胞自己抗原をコードする
Rizwan Ahmed1, Zahra Omidian1, Adebola Giwa2
1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell
|June 1, 2019
まとめ
T細胞とB細胞マーカーの両方を発現する新しい二重発現体 (DE) リンパ球が発見されました. 1型糖尿病では,これらのDEsは強力なCD4T細胞自己抗原を標的とし,自己免疫反応を誘発する.
科学分野:
- 免疫学
- 細胞生物学
- 自己免疫性
背景:
- 適応免疫は伝統的にリンパ球をT細胞とB細胞に分類する.
- T細胞とB細胞の厳格な系統分離は,免疫学の基本的な概念です.
- 1型糖尿病 (T1D) のような自己免疫疾患は,自己抗原に対する異常な免疫反応を含みます.
研究 の 目的:
- 新しいリンパ球群を特定し特徴づけること
- 1型糖尿病の病原性におけるこの新しい細胞の役割を調査する.
- T1Dの自己免疫反応の背後にある分子メカニズムを解明する.
主な方法:
- デュアルエクスプレッサー (DE) リンパ球の識別と特徴付け
- T1D患者のDEsにおけるクローン型レパートリーの分析
- ペプチド-HLA結合を評価するための分子動態シミュレーション
- 合成ペプチドと患者由来細胞を用いたインビトロ刺激アッセイ
- DEクローン型から派生した自己抗体の特徴
主要な成果:
- T細胞受容体 (TCR) とB細胞受容体 (BCR) の両方を表現する,以前未知のリンパ球が特定されました.
- 1型糖尿病では,これらのDEsは,CD4 T細胞オートアンチゲンをコードする特定のクローン型によって支配されています.
- この自己抗原ペプチドは,糖尿病を誘発するHLA- DQ8分子に最適な結合を示す.
- 合成オートアンチゲンペプチドはT1D患者の自己反応性CD4T細胞を刺激する.
- DEクローン型から派生したモノクローナル抗体は自己反応性であり,CD4T細胞機能を阻害する.
結論:
- 適応性免疫細胞の分離は,異なるT細胞とB細胞の系統に絶対的ではありません.
- ダブルエクスプレッサーリンパ球,特に自己反応性クローン型のリンパ球は,タイプ1糖尿病のような自己免疫疾患を誘発する上で重要な役割を果たす可能性があります.
- これらの発見は既存の免疫学的パラダイムに挑戦し,自己免疫病原性への新しい洞察を提供します.
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