Back to Search
Start Over
RhoB Mediates Phosphoantigen Recognition by Vγ9Vδ2 T Cell Receptor.
- Source :
-
Cell reports [Cell Rep] 2016 May 31; Vol. 15 (9), pp. 1973-85. Date of Electronic Publication: 2016 May 19. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Actin Cytoskeleton metabolism
Antigens metabolism
Antigens, CD chemistry
Antigens, CD metabolism
Butyrophilins chemistry
Butyrophilins metabolism
Cell Line, Tumor
Cell Membrane metabolism
Genetic Loci
HEK293 Cells
Humans
Lymphocyte Activation immunology
Models, Biological
Neoplastic Stem Cells metabolism
Phosphorylation
Polymorphism, Single Nucleotide genetics
Protein Binding
Protein Conformation
Protein Multimerization
RNA, Small Interfering metabolism
Receptors, Antigen, T-Cell, gamma-delta metabolism
rhoB GTP-Binding Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 15
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 27210746
- Full Text :
- https://doi.org/10.1016/j.celrep.2016.04.081