Phosphoantigens and butyrophilin 3A1 induce similar intracellular activation signaling in human TCRVγ9+ γδ T lymphocytes

Decaup, Emilie; Duault, Caroline; Bezombes, Christine; Poupot, Mary; Savina, Ariel; Olive, Daniel; Fournié, Jean‐Jacques

doi:10.1016/j.imlet.2014.05.011

Cited by 24 publications

(16 citation statements)

References 15 publications

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“…(anti-CD277) antibody and pAg treatment have induced similar signaling in γδ T cells, suggesting a close overlap between BTN3A-dependent pAg sensing and TCR engagement (106). If the BTN3A complex is not the direct γδ TCR ligand, then what could be?…”

Section: Figurementioning

confidence: 99%

Regulation of Immunity by Butyrophilins

Rhodes

Reith

Trowsdale

2016

Annu. Rev. Immunol.

134

137

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Butyrophilin molecules (commonly contracted to BTN), collectively take their name from the eponymous protein in cow's milk. They are considered to be members of the B7 family of costimulatory receptors, which includes B7.1 (CD80), B7.2 (CD86), and related molecules, such as PD-L1 (B7-H1, CD274), ICOS-L (CD275), and B7-H3 (CD276). These coreceptors modulate T cell responses upon antigen presentation by major histocompatibility complex and cognate αβ T cell receptor engagement. Molecules such as BTN3A1 (CD277), myelin oligodendrocyte glycoprotein, and mouse Skint1 and Btnl2, all members of the butyrophilin family, show greater structural and functional diversity than the canonical B7 receptors. Some butyrophilins mediate complex interactions between antigen-presenting cells and conventional αβ T cells, and others regulate the immune responses of specific γδ T cell subsets by mechanisms that have characteristics of both innate and adaptive immunity.

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Section: Figurementioning

confidence: 99%

Regulation of Immunity by Butyrophilins

Rhodes

Reith

Trowsdale

2016

Annu. Rev. Immunol.

134

137

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“…Activation by mAb 20.1 of TCR-MOP transductants but also of primary responder cells is usually less efficient than PAg-induced activation. Nevertheless, it has been shown for primary γδ T cells that PAg- and mAb 20.1-induced activation are quite similar with respect to TCR-mediated signals and phenotypic changes of the cells ( 92 ). Furthermore, activation by mAb 20.1 is resistant to statins and not accompanied by accumulation of IPP ( 80 , 82 ).…”

Section: Btn3 Is Mandatory For Pag-mediated Activation Of Vγ9vδ2 T Cementioning

confidence: 99%

The VÎ³9VÎ´2 T Cell Antigen Receptor and Butyrophilin-3 A1: Models of Interaction, the Possibility of Co-Evolution, and the Case of Dendritic Epidermal T Cells

Karunakaran

Herrmann

2014

Front. Immunol.

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Most circulating human gamma delta T cells are Vγ9Vδ2 T cells. Their hallmark is the expression of T cell antigen receptors (TCR) whose γ-chains show a Vγ9-JP (Vγ2-Jγ1.2) rearrangement and are paired with Vδ2-containing δ-chains, a dominant TCR configuration, which until recently seemed to occur in primates only. Vγ9Vδ2 T cells respond to phosphoantigens (PAg) such as (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which is produced by many pathogens and isopentenyl pyrophosphate (IPP), which accumulates in certain tumors or cells treated with aminobisphosphonates such as zoledronate. A prerequisite for PAg-induced activation is the contact of Vγ9Vδ2 T cells with cells expressing butyrophilin-3 A1 (BTN3A1). We will first critically review models of how BTN3 might act in PAg-mediated Vγ9Vδ2 T cell activation and then address putative co-evolution of Vγ9, Vδ2, and BTN3 genes. In those rodent and lagomorphs used as animal models, all three genes are lost but a data-base analysis showed that they emerged together with placental mammals. A strong concomitant conservation of functional Vγ9, Vδ2, and BTN3 genes in other species suggests co-evolution of these three genes. A detailed analysis was performed for the new world camelid alpaca (Vicugna pacos). It provides an excellent candidate for a non-primate species with presumably functional Vγ9Vδ2 T cells since TCR rearrangements share features characteristic for PAg-reactive primate Vγ9Vδ2 TCR and proposed PAg-binding sites of BTN3A1 have been conserved. Finally, we analyze the possible functional relationship between the butyrophilin-family member Skint1 and the γδ TCR-V genes used by murine dendritic epithelial T cells (DETC). Among placental mammals, we identify five rodents, the cow, a bat, and the cape golden mole as the only species concomitantly possessing potentially functional homologs of murine Vγ3, Vδ4 genes, and Skint1 gene and suggest to search for DETC like cells in these species.

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“…mAb 20.1 and sc 20.1 activate primary Vγ9Vδ2 T cells and induce a reduction of cell surface mobility of BTN3A1 similar as seen for ABP‐pulsed human cells . TCR proximal signaling of primary cells after stimulation with mAb 20.1 or the PAg BrHPP also shows a high degree of similarity .…”

Section: Introductionmentioning

confidence: 70%

Butyrophilin 3A (BTN3A, CD277)‐specific antibody 20.1 differentially activates Vγ9Vδ2 TCR clonotypes and interferes with phosphoantigen activation

et al. 2017

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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 Vγ9Vδ2 T cells. Here, we compared murine reporter cells transduced with Vγ9Vδ2 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 γ-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 Vγ9Vδ2 T-cell activation, and highlights the complex mode of action of BTN3A-specific antibodies as agents in cancer immunotherapy.

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Phosphoantigens and butyrophilin 3A1 induce similar intracellular activation signaling in human TCRVγ9+ γδ T lymphocytes

Cited by 24 publications

References 15 publications

Regulation of Immunity by Butyrophilins

Regulation of Immunity by Butyrophilins

The VÎ³9VÎ´2 T Cell Antigen Receptor and Butyrophilin-3 A1: Models of Interaction, the Possibility of Co-Evolution, and the Case of Dendritic Epidermal T Cells

Butyrophilin 3A (BTN3A, CD277)‐specific antibody 20.1 differentially activates Vγ9Vδ2 TCR clonotypes and interferes with phosphoantigen activation

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