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

Authors:

• 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
• Gully, Benjamin S.

Details:

Structure, Volume 33, Issue 10, 2025-10-02

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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.