腫瘍浸透性リンパ球に発現する孤児T細胞受容体の抗原識別
Marvin H Gee1, Arnold Han2, Shane M Lofgren3
1Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|December 26, 2017
まとめ
腫瘍の抗原を特定することは,がんの免疫療法にとって極めて重要です. この研究では,腫瘍に浸透するリンパ球のT細胞受容体が,自己抗原を含む特定の標的を見つけるためにスクリーニングされ,がん抗原の発見に役立ちます.
科学分野:
- 免疫学
- 腫瘍学
- 分子生物学
背景:
- 腫瘍に浸透するリンパ球 (TILs) は,抗腫瘍免疫に役割を果たします.
- TILによって認識される特定の抗体は,しばしば不明である.
- TIL抗原の特異性を理解することは,がんの免疫療法の開発の鍵です.
研究 の 目的:
- T細胞受容体 (TCRs) の抗原特異性をヒト大腸がんTILから特定する.
- TCRスクリーニングのための酵母ディスプレイペプチド-MHCライブラリの使用を調査する.
- TILによって認識される新しい腫瘍抗原を発見するために
主な方法:
- ヒト白血球抗原 (pHLA) の酵母ディスプレイライブラリをスクリーニングに使用した.
- 大腸内腺がんのTILからTCRで認識された抗原をスクリーニングした.
- 多様なpHLA-A*02:01ライブラリ内の分析されたTCR選択.
主要な成果:
- 4つのTIL-derived TCRは,pHLAライブラリで強い選択を示した.
- 3つのTCRが 変異しない自己抗原を認識した
- 2つのTCRは,異なる腫瘍で発見されたU2AF2から派生した同じ自己抗原を認識しました.
- TCRは同種の抗原に対して高い特異性を示すことが示された.
結論:
- MHC結合ペプチドの構造情報は,TCR標的を特定するのに十分である.
- この偏見のないスクリーニングアプローチは,腫瘍抗原の識別を容易にする.
- TILによって認識される自己抗原をがん治療で標的とする可能性を裏付けている.
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