English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

The alphabeta TCR has recently been suggested to function as an anisotropic mechanosensor during immune surveillance, converting mechanical energy into a biochemical signal upon specific peptide/MHC ligation of the alphabeta clonotype. The heterodimeric CD3epsilongamma and CD3epsilondelta subunits, each composed of two Ig-like ectodomains, form unique side-to-side hydrophobic interfaces involving their paired G-strands, rigid connectors to their respective transmembrane segments. Those dimers are laterally disposed relative to the alphabeta heterodimer within the TCR complex. In this paper, using structure-guided mutational analysis, we investigate the functional consequences of a striking asymmetry in CD3gamma and CD3delta G-strand geometries impacting ectodomain shape. The uniquely kinked conformation of the CD3gamma G-strand is crucial for maximizing Ag-triggered TCR activation and surface TCR assembly/expression, offering a geometry to accommodate juxtaposition of CD3gamma and TCR beta ectodomains and foster quaternary change that cannot be replaced by the isologous CD3delta subunit's extracellular region. TCRbeta and CD3 subunit protein sequence analyses among Gnathostomata species show that the Cbeta FG loop and CD3gamma subunit coevolved, consistent with this notion. Furthermore, restoration of T cell activation and development in CD3gamma(-/-) mouse T lineage cells by interspecies replacement can be rationalized from structural insights on the topology of chimeric mouse/human CD3epsilondelta dimers. Most importantly, our findings imply that CD3gamma and CD3delta evolved from a common precursor gene to optimize peptide/MHC-triggered alphabeta TCR activation.

Distinctive CD3 Heterodimeric Ectodomain Topologies Maximize Antigen-Triggered Activation of αβ T Cell Receptors