期刊
FRONTIERS IN IMMUNOLOGY
卷 6, 期 -, 页码 1-13出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2015.00441
关键词
T cell receptor; antigen recognition; mechanosensor; catch bond; kinetic proofreading; pre-TCR; thymic development; CD3
类别
资金
- NIH [RO1 AI 100643, AI037581, PO1 GM047467]
The alpha beta TCR was recently revealed to function as a mechanoreceptor. That is, it leverages mechanical energy generated during immune surveillance and at the immunological synapse to drive biochemical signaling following ligation by a specific foreign peptide MHC complex (pMHC). Here, we review the structural features that optimize this transmembrane (TM) receptor for mechanotransduction. Specialized adaptations include (1) the CpFG loop region positioned between V beta and C beta domains that allosterically gates both dynamic T cell receptor (TCR) pMHC bond formation and lifetime; (2) the rigid super p-sheet amalgams of heterodimeric CD3 epsilon gamma and CD3 epsilon delta ectodomain components of the alpha beta TCR complex; (3) the alpha beta TCR subunit connecting peptides linking the extracellular and TM segments, particularly the oxidized CxxC motif in each CD3 heterodimeric subunit that facilitates force transfer through the TM segments and surrounding lipid, impacting cytoplasmic tail conformation; and (4) quaternary changes in the alpha beta TCR complex that accompany pMHC ligation under load. How bioforces foster specific alpha beta TCR-based pMHC discrimination and why dynamic bond formation is a primary basis for kinetic proofreading are discussed. We suggest that the details of the molecular rearrangements of individual alpha beta TCR subunit components can be analyzed utilizing a combination of structural biology, single-molecule FRET, optical tweezers, and nanobiology, guided by insightful atomistic molecular dynamic studies. Finally, we review very recent data showing that the pre-TCR complex employs a similar mechanobiology to that of the alpha beta TCR to interact with self-pMHC ligands, impacting early thymic repertoire selection prior to the CD4(+)CD8(+) double positive thymocyte stage of development.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据