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Cooperative ectodomain interaction among TCRαβ, CD3δɛ and CD3γɛ

The T-cell receptor (TCR) complex comprises of the ligand-binding subunit TCRαβ, and the signaling subunits CD3δɛ, CD3γɛ and CD3ζζ, with the Cα/Cβ in proximity to both CD3δɛ and CD3γɛ extracellularly. Direct measurements of the ectodomain interactions had not been successful, although they are belie...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2021-05, Vol.206 (1_Supplement), p.25-25.08
Main Authors: Yuan, Zhou, Cong, Peiwen, Ge, Chenghao, Natarajan, Aswin, Travaglino, Stefano, Krogsgaard, Michelle, Zhu, Cheng
Format: Article
Language:English
Online Access:Get full text
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Summary:The T-cell receptor (TCR) complex comprises of the ligand-binding subunit TCRαβ, and the signaling subunits CD3δɛ, CD3γɛ and CD3ζζ, with the Cα/Cβ in proximity to both CD3δɛ and CD3γɛ extracellularly. Direct measurements of the ectodomain interactions had not been successful, although they are believed to be important for TCR stability and functionality. Mechanical force has been shown to modulate TCR–ligand interactions. The TCR mechanosensor hypothesis predicts that force-encoded information may transmit from pMHC to CD3 via TCR-CD3 interaction. Evaluating ectodomain interactions among TCRαβ, CD3δɛ and CD3γɛ can help elucidate the TCR triggering mechanism and further guide the design of TCR-based immunotherapy. Using two mechanical based assays, we were able to measure the weak two-dimensional (2D) affinities among ectodomains of human TCRαβ (2B4-LC13), and human CD3δɛ or CD3γɛ and showed catch bond formation where lifetimes of TCRαβ–CD3δɛ and TCRαβ–CD3γɛ bonds are prolonged by forces
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.206.Supp.25.08