Antibody-like recognition of a γδ T cell receptor toward a foreign antigen

Rashleigh, Liam, Venugopal, Hariprasad, Rice, Michael T., Gunasinghe, Sachith D., Sok, Chhon Ling, Gherardin, Nicholas A., Almeida, Catarina F., Van Rhijn, Ildiko, Moody, D. Branch, Godfrey, Dale I., Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522 and Gully, Benjamin S. 2025. Antibody-like recognition of a γδ T cell receptor toward a foreign antigen. Structure 33 10.1016/j.str.2025.07.006

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Abstract

The antigen recognition principles of B cells and αβ T cells have been well described compared to those of the γδ T cell. By way of their specificity conferring receptor (γδTCR), γδ T cells can directly bind proteinaceous antigens. A known γδ T cell and B cell model antigen is phycoerythrin (PE), a light harvesting protein from rhodophytes and cyanobacteria. Here we probed human γδTCR reactivity to PE, in which a Vδ1Vγ5 TCR bound directly to induce proximal signaling and cellular activation. We determined the cryoelectron microscopy (cryo-EM) structure of the γδTCR-phycoerythrin immune complex. We then determined the cryo-EM structures of an antibody fragment and an αβTCR bound to PE. This revealed convergent use of apical aromatic residues to mediate contacts with a common PE epitope. Comparative analyses of the γδTCR revealed multiple antibody-like characteristics, including an enrichment of apical aromatic residues. Our findings reveal further distinct facets of antigen recognition by the γδTCR.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Publisher:	Elsevier
ISSN:	0969-2126
Date of First Compliant Deposit:	12 August 2025
Date of Acceptance:	4 July 2025
Last Modified:	12 Aug 2025 12:48
URI:	https://orca.cardiff.ac.uk/id/eprint/180372

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