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Self-activation of Vγ9Vδ2 T cells by exogenous phosphoantigens involves TCR and butyrophilins

Cellular & Molecular Immunology 2021年第8期18卷 1861-1870页

作者： ChloéLaplagne Laetitia Ligat Juliet Foote Frederic Lopez Jean-Jacques Fournié Camille Laurent Salvatore Valitutti Mary Poupot Inserm UMR1037 Centre de Recherches en Cancérologie de ToulouseToulouseFrance UniversitéToulouse III Paul-Sabatier ToulouseFrance ERL 5294 CNRS ToulouseFrance IUCT-O ToulouseFrance

The high cytotoxic activity of Vγ9Vδ2 T lymphocytes against tumor cells makes them useful candidates in anticancer therapies.However,the molecular mechanism of their activation by phosphoantigens(PAgs)is not completely known.Many studies have depicted the mechanism of Vγ9Vδ2 T-cell activation by PAg-sensed accessory cells,such as immune presenting cells or tumor cells.In this study,we demonstrated that pure resting Vγ9Vδ2 T lymphocytes can self-activate through exogenous PAgs,involving their TCR and the butyrophilins BTN3A1 and BTN2A1.This is the first time that these three molecules,concurrently expressed at the plasma membrane of Vγ9Vδ2 T cells,have been shown to be involved together on the same and unique T cell during PAg activation.Moreover,the use of probucol to stimulate the inhibition of this self-activation prompted us to propose that ABCA-1 could be implicated in the transfer of exogenous PAgs inside Vγ9Vδ2 T cells before activating them through membrane clusters formed byγ9TCR,BTN3A1 and BTN2A1.The self-activation of Vγ9Vδ2 T cells,which leads to self-killing,can therefore participate in the failure ofγδT cell-based therapies with exogenous PAgs and should be taken into account.

关键词： Vγ9Vδ2 T cells phosphoantigen Butyrophilins T-cell receptor

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Vlultifunctional immune responses of HMBPP-specific Jy2Vδ2 T cells in M. tuberculosis and other infections

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Cellular & Molecular Immunology 2013年第1期10卷 58-64页

作者： Zheng W Chen Department of Microbiology and Immunology Center for Primate Biomedical Research University of Illinois College of Medicine Chicago chicago IE 60612: USA

Vy2Vδ2 T （also known as Vy9Vδ2 T） cells exist only in primates, and in humans represent a major yδ T-cell sub-population in the total population of circulating yδ T cells. Results from recent studies suggest that while （E）-4-hydroxy-3-methyl-but-2-enyl pyrophosphate （HMBPP） phosphoantigen from Mycobacterium tuberculosis （Mtb） and other microbes activates and expands primate Vy2Vδ2 T cells, the Vy2Vδ2 T-cell receptor （TCR） recognizes and binds to HMBPP on antigen-presenting cells （APC）. In response to HMBPP stimulus, Vy2V82 TCRs array to form signaling-related nanoclusters or nanodomains during the activation of Vy2V82 T cells. Primary infections with H MBPP-producing pathogens drive the evolution of multieffector functional responses in Vy2Vδ2 T cells, although Vy2V82 T cells display different patterns of responses during the acute and chronic phases of Mtb infection and in other infections. Expanded Vy2Vδ2 T cells in primary Mtb infection can exhibit a broader TCR repertoire and a greater clonal response than previously assumed, with different distribution patterns of Vδ,2Vδ2 T-cell clones in lymphoid and non-lymphoid compartments. Emerging in vivo data suggest that HMBPP activation of Vy2W2 T cells appears to impact other immune cells during infection.

关键词：（E）-4-hydroxy-3-methyl-but-2-enyl pyrophosphate yδ T cell HMBPP human infection phosphoantigen T cell receptor T-cell response tuberculosis

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