Mechanical force matters in early T cell activation

• 成果类型: Article
• 署名作者: Fritzsche, Marco; Kruse, Karsten
• 署名单位: University of Oxford; Kennedy Institute for Rheumatology; Rosalind Franklin Institute; University of Geneva; University of Geneva
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14883
• DOI: 10.1073/pnas.2404748121
• 发表日期: 2024-09-10
• 关键词: ligand recognition; target-cell; receptor; tcr; antigen; DISCRIMINATION; kinetics; complex; show

摘要

Mechanical force has repeatedly been highlighted to be involved in T cell activation. However, the biological significance of mechanical force for T cell receptor signaling remains under active consideration. Here, guided by theoretical analysis, we provide a perspective on how mechanical forces between a T cell and an antigen-presenting cell can influence the bond of a single T cell receptor major histocompatibility complex during early T cell activation. We point out that the lifetime of T cell receptor bonds and thus the degree of their phosphorylation which is essential for T cell activation depends considerably on the T cell receptor rigidity and the average magnitude and frequency of an applied oscillatory force. Such forces could be, for example, produced by protrusions like microvilli during early T cell activation or invadosomes during full T cell activation. These features are suggestive of mechanical force being exploited by T cells to advance self-nonself discrimination in early T cell activation.