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T細胞認識のペプチド-MHC特異性を分解する

Michael E Birnbaum¹, Juan L Mendoza², Dhruv K Sethi³

¹Departments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.

|May 27, 2014

まとめ

T細胞受容体 (TCRs) は交叉反応性を発揮し,主要な組織適合性複合体 (MHC) 分子が提示する多様なペプチド抗原を認識します. この研究は,TCR認識における保存された構造的モチーフを明らかにし,微生物および自己リガンドの識別を可能にします.

科学分野:

免疫学免疫学とは
分子生物学は分子生物学である.
構造生物学構造生物学とは

背景:

T細胞受容体 (TCR) は,T細胞レパートリー多様性を超えた,メジャー・ヒストコンパティビリティ・コンプレックス (MHC) が提示するペプチドの広大な宇宙を認識しなければならない.
この認識のためのメカニズムとしてTCRのクロス反応性が仮説化されているが,実験的検証は限られている.

研究の目的:

TCRのクロス反応性の性質と範囲を実験的に測定する.
TCRによって認識されるMHC呈現ペプチドリガンドを識別するためのシステムを開発する.
ヒトの自己免疫性TCRsのための微生物と自己リガンドを計算的に識別する.

主な方法:

TCR選択のための酵母表示ペプチド-MHCライブラリを使用しました.
選択されたペプチド-MHCリガンドを分析するために深層配列を解析した.
TCR認識モチーフに基づく計算方法を開発しました.

主要な成果:

マウスとヒトの5つの異なるTCRに対して,何百もの反応性ペプチドを特定した.
既知の抗原に似ている,選択されたペプチドの保存されたTCR認識モチーフを観察した.
自動免疫TCRsのための活性化微生物および自己リガンドの実証された計算識別.

結論:

TCRのクロスリアクティビティのメカニズム的基礎は,構造的な認識面が保存されていることを意味します.
この保存された認識は,多様な外来および自己抗原の効果的な監視を可能にします.
非同類ペプチドの劣化認識は,広範な抗原監視には必要ありません.

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