Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
16 Jul 2024
16 Jul 2024
Historique:
received:
13
09
2023
accepted:
11
06
2024
medline:
17
7
2024
pubmed:
17
7
2024
entrez:
16
7
2024
Statut:
aheadofprint
Résumé
Butyrophilin (BTN) molecules are emerging as key regulators of T cell immunity; however, how they trigger cell-mediated responses is poorly understood. Here, the crystal structure of a gamma-delta T cell antigen receptor (γδTCR) in complex with BTN2A1 revealed that BTN2A1 engages the side of the γδTCR, leaving the apical TCR surface bioavailable. We reveal that a second γδTCR ligand co-engages γδTCR via binding to this accessible apical surface in a BTN3A1-dependent manner. BTN2A1 and BTN3A1 also directly interact with each other in cis, and structural analysis revealed formation of W-shaped heteromeric multimers. This BTN2A1-BTN3A1 interaction involved the same epitopes that BTN2A1 and BTN3A1 each use to mediate the γδTCR interaction; indeed, locking BTN2A1 and BTN3A1 together abrogated their interaction with γδTCR, supporting a model wherein the two γδTCR ligand-binding sites depend on accessibility to cryptic BTN epitopes. Our findings reveal a new paradigm in immune activation, whereby γδTCRs sense dual epitopes on BTN complexes.
Identifiants
pubmed: 39014161
doi: 10.1038/s41590-024-01892-z
pii: 10.1038/s41590-024-01892-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1184906
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1165467
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1117766
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 2008913
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1194263
Organisme : Cancer Council Victoria
ID : 1126866
Organisme : Department of Education and Training | Australian Research Council (ARC)
ID : DP230102753
Organisme : Department of Education and Training | Australian Research Council (ARC)
ID : CE140100011
Organisme : Department of Education and Training | Australian Research Council (ARC)
ID : DE210100705
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
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