Molecular design of the γδT cell receptor ectodomain encodes biologically fit ligand recognition in the absence of mechanosensing
Robert J. Mallis, Jonathan S. Duke‐Cohan, Dibyendu Kumar Das, Aoi Akitsu, Adrienne Luoma, Debasis Banik, Hannah M. Stephens, Paul W. Tetteh, Caitlin D. Castro, Sophie Krahnke, Rebecca E. Hussey, Brian Lawney, Kristine N. Brazin, Pedro A. Reche, Wonmuk Hwang, Erin J. Adams, Matthew J. Lang, Ellis L. Reinherz
Abstract
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.