@article{TEXTUAL,
      recid = {9656},
      author = {Mallis, Robert J. and Duke-Cohan, Jonathan S. and Das,  Dibyendu Kumar and Akitsu, Aoi and Luoma, Adrienne M. and  Banik, Debasis and Stephens, Hannah M. and Tetteh, Paul W.  and Castro, Caitlin D. and Krahnke, Sophie and Hussey,  Rebecca E. and Lawney, Brian and Brazin, Kristine N. and  Reche, Pedro A. and Hwang, Wonmuk and Adams, Erin J. and  Lang, Matthew J. and Reinherz, Ellis L.},
      title = {Molecular design of the γδT cell receptor ectodomain  encodes biologically fit ligand recognition in the absence  of mechanosensing},
      journal = {PNAS},
      address = {2021-06-25},
      number = {TEXTUAL},
      abstract = {High-acuity αβT cell receptor (TCR) recognition of  peptides bound to major histocompatibility complex  molecules (pMHCs) requires mechanosensing, a process  whereby piconewton (pN) bioforces exert physical load on  αβTCR–pMHC bonds to dynamically alter their lifetimes and  foster digital sensitivity cellular signaling. While  mechanotransduction is operative for both αβTCRs and  pre-TCRs within the αβT lineage, its role in γδT cells is  unknown. Here, we show that the human DP10.7 γδTCR specific  for the sulfoglycolipid sulfatide bound to CD1d only  sustains a significant load and undergoes force-induced  structural transitions when the binding interface-distal γδ  constant domain (C) module is replaced with that of αβ. The  chimeric γδ–αβTCR also signals more robustly than does the  wild-type (WT) γδTCR, as revealed by RNA-sequencing  (RNA-seq) analysis of TCR-transduced Rag2<sup>−/−</sup>  thymocytes, consistent with structural, single-molecule,  and molecular dynamics studies reflective of γδTCRs as  mediating recognition via a more canonical  immunoglobulin-like receptor interaction. Absence of  robust, force-related catch bonds, as well as γδTCR  structural transitions, implies that γδT cells do not use  mechanosensing for ligand recognition. This distinction is  consonant with the fact that their innate-type ligands,  including markers of cellular stress, are expressed at a  high copy number relative to the sparse pMHC ligands of αβT  cells arrayed on activating target cells. We posit that  mechanosensing emerged over ∼200 million years of  vertebrate evolution to fulfill indispensable adaptive  immune recognition requirements for pMHC in the αβT cell  lineage that are unnecessary for the γδT cell lineage  mechanism of non-pMHC ligand detection.},
      url = {http://knowledge.uchicago.edu/record/9656},
}