Structure of a fully assembled γδ T cell antigen receptor

Benjamin S. Gully, João Ferreira Fernandes, Sachith D. Gunasinghe, Mai T. Vuong, Yuan Lui, Michael T. Rice, Liam Rashleigh, Chan-sien Lay, Dene R. Littler, Sumana Sharma, Ana Mafalda Santos, Hariprasad Venugopal, Jamie Rossjohn () and Simon J. Davis ()
Additional contact information
Benjamin S. Gully: Monash University
João Ferreira Fernandes: University of Oxford
Sachith D. Gunasinghe: Monash University
Mai T. Vuong: University of Oxford
Yuan Lui: University of Oxford
Michael T. Rice: Monash University
Liam Rashleigh: Monash University
Chan-sien Lay: Monash University
Dene R. Littler: Monash University
Sumana Sharma: University of Oxford
Ana Mafalda Santos: University of Oxford
Hariprasad Venugopal: Monash University
Jamie Rossjohn: Monash University
Simon J. Davis: University of Oxford

Nature, 2024, vol. 634, issue 8034, 729-736

Abstract: Abstract T cells in jawed vertebrates comprise two lineages, αβ T cells and γδ T cells, defined by the antigen receptors they express—that is, αβ and γδ T cell receptors (TCRs), respectively. The two lineages have different immunological roles, requiring that γδ TCRs recognize more structurally diverse ligands1. Nevertheless, the receptors use shared CD3 subunits to initiate signalling. Whereas the structural organization of αβ TCRs is understood2,3, the architecture of γδ TCRs is unknown. Here, we used cryogenic electron microscopy to determine the structure of a fully assembled, MR1-reactive, human Vγ8Vδ3 TCR–CD3δγε2ζ2 complex bound by anti-CD3ε antibody Fab fragments4,5. The arrangement of CD3 subunits in γδ and αβ TCRs is conserved and, although the transmembrane α-helices of the TCR-γδ and -αβ subunits differ markedly in sequence, packing of the eight transmembrane-helix bundles is similar. However, in contrast to the apparently rigid αβ TCR2,3,6, the γδ TCR exhibits considerable conformational heterogeneity owing to the ligand-binding TCR-γδ subunits being tethered to the CD3 subunits by their transmembrane regions only. Reducing this conformational heterogeneity by transfer of the Vγ8Vδ3 TCR variable domains to an αβ TCR enhanced receptor signalling, suggesting that γδ TCR organization reflects a compromise between efficient signalling and the ability to engage structurally diverse ligands. Our findings reveal the marked structural plasticity of the TCR on evolutionary timescales, and recast it as a highly versatile receptor capable of initiating signalling as either a rigid or flexible structure.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-07920-0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:634:y:2024:i:8034:d:10.1038_s41586-024-07920-0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-07920-0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().