Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 47, Issue 6, Pages 982-992Publisher
WILEY
DOI: 10.1002/eji.201646818
Keywords
Butyrophilin; Human gamma delta T cells; Phosphoantigen; T-cell activation; T-cell receptor
Categories
Funding
- Wilhelm-Sander-Stiftung Grant [20013.907.1]
- DAAD
- Fondation pour la Recherche Medicale [Equipe FRM DEQ20140329534]
- International Collaboration Seedcorn Fund
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Phosphoantigens (PAgs)-like HMBPP ((E)-4-hydroxy-3-methyl-but-2-enyl diphosphate) and butyrophilin 3 (BTN3A, CD277)-specific monoclonal antibody 20.1 induce TCR-mediated activation of V gamma 9V delta 2 T cells. Here, we compared murine reporter cells transduced with V gamma 9V delta 2 TCRs G115, D1C55, and MOP for the activation in culture with human RAJI cells and PAgs or mAb 20.1 and its single-chain (sc) derivative. All transductants responded readily to PAg but only TCR MOP gamma-chain-expressing cells responded to mAb/sc 20.1. Furthermore, both antagonist and agonist mAb and sc of the agonist mAb inhibited the PAg response of TCR-transduced murine reporter cells. These findings suggest that, in contrast to stimulation by physiological stimulators (PAg), the responsiveness to mAb 20.1 depends strongly on CDR3 sequences of the TCR, and that mAb 20.1 can interfere with the PAg-response. Mouse or human origin of reporter cells might affect the mAb 20.1 response since all three TCR-mediated mAb 20.1-induced activation of TCR-transduced Jurkat cells. The pronounced differences between PAg and mAb 20.1-induced activation observed here help to understand the often contradictory published data. This study provides novel perspectives on the physiological mechanism of V gamma 9V delta 2 T-cell activation, and highlights the complex mode of action of BTN3A-specific antibodies as agents in cancer immunotherapy.
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