Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers.
Nat Immunol
; 25(8): 1355-1366, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-39014161
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Antígenos de Linfocitos T gamma-delta
/
Butirofilinas
Límite:
Humans
Idioma:
En
Revista:
Nat Immunol
/
Nat. immunol
/
Nature immunology
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Australia