関連する実験動画

Updated: Feb 7, 2026

A High Throughput MHC II Binding Assay for Quantitative Analysis of Peptide Epitopes

A High Throughput MHC II Binding Assay for Quantitative Analysis of Peptide Epitopes

Published on: March 25, 2014

ペプチド-MHC結合からT細胞受容体シグナルを分離する構造的メカニズムの分離

Leah V Sibener¹, Ricardo A Fernandes², Elizabeth M Kolawole³

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

|July 28, 2018

まとめ

高親和性T細胞受容体 (TCR) とペプチド-MHC (pMHC) の相互作用は非刺激的かもしれない. この研究は,T細胞のシグナル伝達と免疫療法において重要なTCR-pMHC相互作用の活性化における"キャッチボンド"を明らかにした.

科学分野:

免疫学
バイオ物理学
構造生物学

背景:

T細胞受容体 (TCR) のシグナリング強度は,典型的にはペプチド-MHC (pMHC) 結合親和と相関する.
しかし,T細胞活性化につながらない高親和のTCR-pMHC相互作用は,ヒトT細胞のレパートリーで頻繁に観察されています.

研究の目的:

強力なpMHC結合にもかかわらず活性化に耐性のあるTCRの基礎にある分子機構を調査する.
T細胞結合とT細胞信号の結合を制御する新しいパラメータを特定する.

主な方法:

TCRアゴニストを特定するための酵母pMHCディスプレイ
TCR-pMHC相互作用を分析するための単一分子力測定 (SMFM)
TCR-pMHCの解約ダイナミクスをモデル化するための分子ダイナミクス (MD) シミュレーション

主要な成果:

3Dの親和性,2Dの停留時間,および結晶構造の分析は,刺激性および非刺激性TCR-pMHC相互作用の違いを完全に説明できませんでした.
接触部位からのCD45排除と相関するTCR- pMHC相互作用の活性化中にキャッチボンドの出現が確認された.
MDシミュレーションでは,TCR-pMHCインターフェイスでキャッチボンドを取得することによって,アゴニストと非アゴニストリガンドを区別しました.

結論:

捕獲ボンドは,TCRの結合親和性をシグナリング結果と結びつける重要なパラメータです.
キャッチボンドの理解は,免疫療法の開発におけるTCRと抗原工学の新しい道を開きます.
この発見は,T細胞の活性化と免疫応答の調節に関するメカニズム的理解を前進させる.

キーワード:

CD45 について MHC TCR についてキャッチボンドリンガンド差別分子動力学シグナリング構造

さらに関連する動画

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis

Published on: October 15, 2021

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding

Published on: June 9, 2017

関連する概念動画

What is Cell Signaling?

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.

Cell-surface Signaling

Cell-surface Signaling

Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.

Yeast Signaling

Yeast Signaling

Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...

Internal Receptors

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.

Ligand Binding and Linkage

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...

Signal Sequences and Sorting Receptors

Signal Sequences and Sorting Receptors

Signal sequences are short amino acid sequences that guide newly synthesized proteins to their proper location within the cell. Classical signal sequences are fifteen to sixty amino acids long and present at the N-terminus of a polypeptide chain. Each signal sequence has a conserved segment of basic residues towards their N terminus, a hydrophobic core, and a C-terminus rich in polar residues. The C-terminus also contains a signal cleavage site and features a -3 -1 sequence motif. The -3-1...