Accumulation of Dynamic Catch bonds between TCR and agonist pMHC triggers T cell signaling and its s

• 作 者: Wei Chen Baoyu Liu Ryan J.Martinez Brian D.Evovald Jizhong Lou Cheng Zhu
• 机 构: CoulterDepartmentofBiomedicalEngineeringDepartmentofMicrobiologyandImmunology,EmoryUniversitySchoolo
• 出 处: 中国化学会第三届全国生物物理化学会议暨国际华人生物物理化学发展论坛
• 发表日期: 2014年7期

Appropriate interaction between the T-cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) initiates adaptive immune responses,but the mechanism of how such interactions under force induce T cell signaling is unclear.We first show that force prolongs lifetimes of single TCR-pMHC bonds for agonists (catch bonds) but shortens those for antagonists (slip bonds).Both magnitude and duration of force are important,as the highest Ca2+ responses were induced by 10 pN via both pMHC catch bonds whose lifetime peaks at this force.High Ca2+ levels require early and rapid accumulation of bond lifetimes,whereas short-lived bonds that slow early accumulation of lifetimes correspond to low Ca2+ responses.Our data support a model in which force on the TCR induces signaling events depending on its magnitude,duration,frequency,and timing,such that agonists form catch bonds that trigger the T cell digitally,whereas antagonists form slip bonds that fail to activate.