RhoB Mediates Phosphoantigen Recognition by Vγ9Vδ2 T Cell Receptor

Zsolt Sebestyen; Wouter Scheper; Anna Vyborova; Siyi Gu; Zuzana Rychnavska; Marleen Schiffler; Astrid Cleven; Coraline Chéneau; Martje van Noorden; Cassie-Marie Peigné; Daniel Olive; Robert Jan Lebbink; Rimke Oostvogels; Tuna Mutis; Gerrit Jan Schuurhuis; Erin J Adams; Emmanuel Scotet; Jürgen Kuball

doi:10.1016/j.celrep.2016.04.081

RhoB Mediates Phosphoantigen Recognition by Vγ9Vδ2 T Cell Receptor

Zsolt Sebestyen, Wouter Scheper, Anna Vyborova, Siyi Gu, Zuzana Rychnavska, Marleen Schiffler, Astrid Cleven, Coraline Chéneau, Martje van Noorden, Cassie-Marie Peigné, Daniel Olive, Robert Jan Lebbink, Rimke Oostvogels, Tuna Mutis, Gerrit Jan Schuurhuis, Erin J Adams, Emmanuel Scotet, Jürgen Kuball

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Abstract

Human Vγ9Vδ2 T cells respond to tumor cells by sensing elevated levels of phosphorylated intermediates of the dysregulated mevalonate pathway, which is translated into activating signals by the ubiquitously expressed butyrophilin A1 (BTN3A1) through yet unknown mechanisms. Here, we developed an unbiased, genome-wide screening method that identified RhoB as a critical mediator of Vγ9Vδ2 TCR activation in tumor cells. Our results show that Vγ9Vδ2 TCR activation is modulated by the GTPase activity of RhoB and its redistribution to BTN3A1. This is associated with cytoskeletal changes that directly stabilize BTN3A1 in the membrane, and the subsequent dissociation of RhoB from BTN3A1. Furthermore, phosphoantigen accumulation induces a conformational change in BTN3A1, rendering its extracellular domains recognizable by Vγ9Vδ2 TCRs. These complementary events provide further evidence for inside-out signaling as an essential step in the recognition of tumor cells by a Vγ9Vδ2 TCR.

Original language	English
Pages (from-to)	1973-1985
Number of pages	13
Journal	Cell Reports [E]
Volume	15
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2016.04.081
Publication status	Published - 2016

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Sebestyen, Z., Scheper, W., Vyborova, A., Gu, S., Rychnavska, Z., Schiffler, M., Cleven, A., Chéneau, C., van Noorden, M., Peigné, C.-M., Olive, D., Lebbink, R. J., Oostvogels, R., Mutis, T., Schuurhuis, G. J., Adams, E. J., Scotet, E., & Kuball, J. (2016). RhoB Mediates Phosphoantigen Recognition by Vγ9Vδ2 T Cell Receptor. Cell Reports [E], 15(9), 1973-1985. https://doi.org/10.1016/j.celrep.2016.04.081

@article{bd5ed0e5857a4330bb731ef7341b7db5,

title = "RhoB Mediates Phosphoantigen Recognition by Vγ9Vδ2 T Cell Receptor",

abstract = "Human Vγ9Vδ2 T cells respond to tumor cells by sensing elevated levels of phosphorylated intermediates of the dysregulated mevalonate pathway, which is translated into activating signals by the ubiquitously expressed butyrophilin A1 (BTN3A1) through yet unknown mechanisms. Here, we developed an unbiased, genome-wide screening method that identified RhoB as a critical mediator of Vγ9Vδ2 TCR activation in tumor cells. Our results show that Vγ9Vδ2 TCR activation is modulated by the GTPase activity of RhoB and its redistribution to BTN3A1. This is associated with cytoskeletal changes that directly stabilize BTN3A1 in the membrane, and the subsequent dissociation of RhoB from BTN3A1. Furthermore, phosphoantigen accumulation induces a conformational change in BTN3A1, rendering its extracellular domains recognizable by Vγ9Vδ2 TCRs. These complementary events provide further evidence for inside-out signaling as an essential step in the recognition of tumor cells by a Vγ9Vδ2 TCR.",

author = "Zsolt Sebestyen and Wouter Scheper and Anna Vyborova and Siyi Gu and Zuzana Rychnavska and Marleen Schiffler and Astrid Cleven and Coraline Ch{\'e}neau and {van Noorden}, Martje and Cassie-Marie Peign{\'e} and Daniel Olive and Lebbink, {Robert Jan} and Rimke Oostvogels and Tuna Mutis and Schuurhuis, {Gerrit Jan} and Adams, {Erin J} and Emmanuel Scotet and J{\"u}rgen Kuball",

year = "2016",

doi = "10.1016/j.celrep.2016.04.081",

language = "English",

volume = "15",

pages = "1973--1985",

journal = "Cell Reports [E]",

issn = "2211-1247",

publisher = "Cell Press",

number = "9",

}

Sebestyen, Z, Scheper, W, Vyborova, A, Gu, S, Rychnavska, Z, Schiffler, M, Cleven, A, Chéneau, C, van Noorden, M, Peigné, C-M, Olive, D, Lebbink, RJ, Oostvogels, R, Mutis, T, Schuurhuis, GJ, Adams, EJ, Scotet, E & Kuball, J 2016, 'RhoB Mediates Phosphoantigen Recognition by Vγ9Vδ2 T Cell Receptor', Cell Reports [E], vol. 15, no. 9, pp. 1973-1985. https://doi.org/10.1016/j.celrep.2016.04.081

TY - JOUR

T1 - RhoB Mediates Phosphoantigen Recognition by Vγ9Vδ2 T Cell Receptor

AU - Sebestyen, Zsolt

AU - Scheper, Wouter

AU - Vyborova, Anna

AU - Gu, Siyi

AU - Rychnavska, Zuzana

AU - Schiffler, Marleen

AU - Cleven, Astrid

AU - Chéneau, Coraline

AU - van Noorden, Martje

AU - Peigné, Cassie-Marie

AU - Olive, Daniel

AU - Lebbink, Robert Jan

AU - Oostvogels, Rimke

AU - Mutis, Tuna

AU - Schuurhuis, Gerrit Jan

AU - Adams, Erin J

AU - Scotet, Emmanuel

AU - Kuball, Jürgen

PY - 2016

Y1 - 2016

N2 - Human Vγ9Vδ2 T cells respond to tumor cells by sensing elevated levels of phosphorylated intermediates of the dysregulated mevalonate pathway, which is translated into activating signals by the ubiquitously expressed butyrophilin A1 (BTN3A1) through yet unknown mechanisms. Here, we developed an unbiased, genome-wide screening method that identified RhoB as a critical mediator of Vγ9Vδ2 TCR activation in tumor cells. Our results show that Vγ9Vδ2 TCR activation is modulated by the GTPase activity of RhoB and its redistribution to BTN3A1. This is associated with cytoskeletal changes that directly stabilize BTN3A1 in the membrane, and the subsequent dissociation of RhoB from BTN3A1. Furthermore, phosphoantigen accumulation induces a conformational change in BTN3A1, rendering its extracellular domains recognizable by Vγ9Vδ2 TCRs. These complementary events provide further evidence for inside-out signaling as an essential step in the recognition of tumor cells by a Vγ9Vδ2 TCR.

AB - Human Vγ9Vδ2 T cells respond to tumor cells by sensing elevated levels of phosphorylated intermediates of the dysregulated mevalonate pathway, which is translated into activating signals by the ubiquitously expressed butyrophilin A1 (BTN3A1) through yet unknown mechanisms. Here, we developed an unbiased, genome-wide screening method that identified RhoB as a critical mediator of Vγ9Vδ2 TCR activation in tumor cells. Our results show that Vγ9Vδ2 TCR activation is modulated by the GTPase activity of RhoB and its redistribution to BTN3A1. This is associated with cytoskeletal changes that directly stabilize BTN3A1 in the membrane, and the subsequent dissociation of RhoB from BTN3A1. Furthermore, phosphoantigen accumulation induces a conformational change in BTN3A1, rendering its extracellular domains recognizable by Vγ9Vδ2 TCRs. These complementary events provide further evidence for inside-out signaling as an essential step in the recognition of tumor cells by a Vγ9Vδ2 TCR.

U2 - 10.1016/j.celrep.2016.04.081

DO - 10.1016/j.celrep.2016.04.081

M3 - Article

C2 - 27210746

SN - 2211-1247

VL - 15

SP - 1973

EP - 1985

JO - Cell Reports [E]

JF - Cell Reports [E]

IS - 9

ER -

RhoB Mediates Phosphoantigen Recognition by Vγ9Vδ2 T Cell Receptor

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