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Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human ?? T-cell subset.

ABSTRACT: Human peripheral V?9V?2 T cells are activated by phosphorylated metabolites (phosphoagonists [PAg]) of the mammalian mevalonate or the microbial desoxyxylulose-phosphate pathways accumulated by infected or metabolically distressed cells. The underlying mechanisms are unknown. We show that treatment of nonsusceptible target cells with antibody 20.1 against CD277, a member of the extended B7 superfamily related to butyrophilin, mimics PAg-induced V?9V?2 T-cell activation and that the V?9V?2 T-cell receptor is implicated in this effect. V?9V?2 T-cell activation can be abrogated by exposing susceptible cells (tumor and mycobacteria-infected cells, or aminobisphosphonate-treated cells with up-regulated PAg levels) to antibody 103.2 against CD277. CD277 knockdown and domain-shuffling approaches confirm the key implication of the CD277 isoform BTN3A1 in PAg sensing by V?9V?2 T cells. Fluorescence recovery after photobleaching (FRAP) experiments support a causal link between intracellular PAg accumulation, decreased BTN3A1 membrane mobility, and ensuing V?9V?2 T-cell activation. This study demonstrates a novel role played by B7-like molecules in human ?? T-cell antigenic activation and paves the way for new strategies to improve the efficiency of immunotherapies using V?9V?2 T cells.

SUBMITTER: Harly C

PROVIDER: S-EPMC3679641 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset.

Harly Christelle C Guillaume Yves Y Nedellec Steven S Peigné Cassie-Marie CM Mönkkönen Hannu H Mönkkönen Jukka J Li Jianqiang J Kuball Jürgen J Adams Erin J EJ Netzer Sonia S Déchanet-Merville Julie J Léger Alexandra A Herrmann Thomas T Breathnach Richard R Olive Daniel D Bonneville Marc M Scotet Emmanuel E

Blood 20120705 11

Human peripheral Vγ9Vδ2 T cells are activated by phosphorylated metabolites (phosphoagonists [PAg]) of the mammalian mevalonate or the microbial desoxyxylulose-phosphate pathways accumulated by infected or metabolically distressed cells. The underlying mechanisms are unknown. We show that treatment of nonsusceptible target cells with antibody 20.1 against CD277, a member of the extended B7 superfamily related to butyrophilin, mimics PAg-induced Vγ9Vδ2 T-cell activation and that the Vγ9Vδ2 T-cell ...[more]

PMID: 22767497

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Dataset Information

Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human ?? T-cell subset.

Publications

Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset.

Similar Datasets

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