Filtern
Volltext vorhanden
- ja (11)
Gehört zur Bibliographie
- ja (11)
Dokumenttyp
Sprache
- Englisch (11) (entfernen)
Schlagworte
- T cells (3)
- phosphoantigen (3)
- BTN3 (2)
- alpaca (2)
- butyrophilin (2)
- butyrophilin 3 (2)
- cell staining (2)
- evolution (2)
- γδ T cell (2)
- ABCG2 (1)
- BTN (1)
- BTN2 (1)
- BTN2A1 (1)
- BTN3A1 (1)
- DETC (1)
- Dendritische Zelle (1)
- Krebs <Medizin> (1)
- NRF2 (1)
- Skint1 (1)
- T cell receptor (1)
- TRDV2 (1)
- TRGV9 (1)
- Vγ9Vδ2 (1)
- Vγ9Vδ2 T cell (1)
- antigen presentation (1)
- binding analysis (1)
- butyrophilin 2A1 (1)
- butyrophilins (1)
- co-evolution (1)
- coevolution (1)
- cytotoxic T cells (1)
- fluorescence-activated cell sorting (1)
- gammadelta T cells (1)
- glycolipids (1)
- human (1)
- immune therapy (1)
- immunosurveillance (1)
- interleukins (1)
- lipids (1)
- lymph nodes (1)
- lymphomas (1)
- major histocompatibility complex (1)
- mevalonate pathway (1)
- mouse models (1)
- nine-banded armadillo (1)
- oligomers (1)
- phosphoantigens (1)
- placental mammals (1)
- surfactants (1)
- tumor (1)
- γδ T cells (1)
- γδ TCR (1)
Butyrophilin (BTN)–3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg sensing remain largely unknown. Here, we establish three mechanistic principles of PAg-mediated γδ T cell activation. First, in humans, following PAg binding to the intracellular BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the extracellular V-domain of BTN3A2/BTN3A3. Moreover, the localization of both protein domains on different chains of the BTN3A homo-or heteromers is essential for efficient PAg-mediated activation. Second, the formation of BTN3A homo-or heteromers, which differ in intracellular trafficking and conformation, is controlled by molecular interactions between the juxtamembrane regions of the BTN3A chains. Finally, the ability of PAg not simply to bind BTN3A-B30.2, but to promote its subsequent interaction with the BTN2A1-B30.2 domain, is essential for T-cell activation. Defining these determinants of cooperation and the division of labor in BTN proteins improves our understanding of PAg sensing and elucidates a mode of action that may apply to other BTN family members.