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PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8(+) T cells

Karwacz, K; Bricogne, C; MacDonald, D; Arce, F; Bennett, CL; Collins, M; Escors, D; (2011) PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8(+) T cells. EMBO Molecular Medicine , 3 (10) 581 - 592. 10.1002/emmm.201100165. Green open access

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Abstract

T cell receptor (TCR) down-modulation after antigen presentation is a fundamental process that regulates TCR signal transduction. Current understanding of this process is that intrinsic TCR/CD28 signal transduction leads to TCR down-modulation. Here, we show that the interaction between programmed cell death 1 ligand 1 (PD-L1) on dendritic cells (DCs) and programmed death 1 (PD-1) on CD8 T cells contributes to ligand-induced TCR down-modulation. We provide evidence that this occurs via Casitas B-lymphoma (Cbl)-b E3 ubiquitin ligase up-regulation in CD8 T cells. Interference with PD-L1/PD-1 signalling markedly inhibits TCR down-modulation leading to hyper-activated, proliferative CD8 T cells as assessed in vitro and in vivo in an arthritis model. PD-L1 silencing accelerates anti-tumour immune responses and strongly potentiates DC anti-tumour capacities, when combined with mitogen-activated kinase (MAPK) modulators that promote DC activation.

Type: Article
Title: PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8(+) T cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/emmm.201100165
Publisher version: http://doi.org/10.1002/emmm.201100165
Language: English
Additional information: The journal publishes articles under the Creative Commons Attribution CC BY 4.0 License. Copyright on any article published by the journal is retained by the author(s).
Keywords: Cbl, Dendritic Cells, PD‐1, PD‐L1, TCR
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: https://discovery.ucl.ac.uk/id/eprint/1316966
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