The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells

Roncagalli, Romain; Cucchetti, Margot; Jarmuzynski, Nicolas; Grégoire, Claude; Bergot, Elise; Audebert, Stéphane; Baudelet, Emilie; Menoita, Marisa Goncalves; Joachim, Anaïs; Durand, Stephane; Suchánek, Miloslav; Fiore, Frédéric Di; Zhang, Lichen; Liang, Yinming; Camoin, Luc; Malissen, Marie; Malissen, Bernard

doi:10.1084/jem.20160579

Cited by 70 publications

(111 citation statements)

References 55 publications

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“…It will be intriguing to know of CD28‐dependent glucokinase expression also regulates Treg cell migration to tumours. CD28 is also a major activator of the nuclear factor‐ κ B pathway, which may be more central to its co‐stimulatory function …”

Section: Pi3kδ Downstream Of Core T‐cell Receptorsmentioning

confidence: 99%

Phosphoinositide 3‐kinase δ is a regulatory T‐cell target in cancer immunotherapy

Lim

Okkenhaug

2019

Immunology

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Summary Tumour infiltration by regulatory T (Treg) cells contributes to suppression of the anti‐tumour immune response, which limits the efficacy of immune‐mediated cancer therapies. The phosphoinositide 3‐kinase (PI3K) pathway has key roles in mediating the function of many immune cell subsets, including Treg cells. Treg function is context‐dependent and depends on input from different cell surface receptors, many of which can activate the PI3K pathway. In this review, we explore how PI3Kδ contributes to signalling through several major immune cell receptors, including the T‐cell receptor and co‐stimulatory receptors such as CD28 and ICOS, but is antagonized by the immune checkpoint receptors CTLA‐4 and PD‐1. Understanding how PI3Kδ inhibition affects Treg signalling events will help to inform how best to use PI3Kδ inhibitors in clinical cancer treatment.

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Section: Pi3kδ Downstream Of Core T‐cell Receptorsmentioning

confidence: 99%

Phosphoinositide 3‐kinase δ is a regulatory T‐cell target in cancer immunotherapy

Lim

Okkenhaug

2019

Immunology

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“…When CD28 signalling is blocked at the time of T‐cell priming, T‐cell activation is suppressed and this prevents Tfh cell differentiation in vivo . CD28 co‐stimulation depends upon the RLTPR, a scaffold protein that links CD28 to the CARD11/CARMA1 cytosolic adapter and to the nuclear factor‐ κ B (NF‐ κ B) pathway . Mice and humans deficient in RLTPR have very few Tfh cells and this is associated with defects in activation‐induced expression of CD40L, ICOS and RelA phosphorylation (indicative of impaired NF‐ κ B signalling) .…”

Section: The Importance Of Co‐receptor Signals In Tfh Cell Differentimentioning

confidence: 99%

“…50,51 Mice and humans deficient in RLTPR have very few Tfh cells and this is associated with defects in activation-induced expression of CD40L, ICOS and RelA phosphorylation (indicative of impaired NF-jB signalling). 50,51 Once T cells have acquired CXCR5 expression and migrated to Bcell follicles the role of CD28 is less clear. Tfh cell differentiation can occur when CD28 co-stimulation is inhibited after priming in vivo by administration of CTLA-4immunoglobulin, a treatment that would also prevent CTLA-4 signalling.…”

Section: Presentation Of Antigen By B Cellsmentioning

confidence: 99%

Signals that drive T follicular helper cell formation

Webb

Linterman

2017

Immunology

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SummaryT follicular helper (Tfh) cells are a distinct type of CD4 + T cell specialized in providing help to B cells during the germinal centre (GC) reaction. As such, they are critical determinants of the quality of an antibody response following antigen challenge. Excessive production of Tfh cells can result in autoimmunity whereas too few can result in inadequate protection from infection. Hence, their differentiation and maintenance must be tightly regulated to ensure appropriate but limited help to B cells. Unlike the majority of other CD4 + T-cell subsets, Tfh cell differentiation occurs in three phases defined by their anatomical location. During each phase of differentiation the emerging Tfh cells express distinct patterns of coreceptors, which work together with the T-cell receptor (TCR) to drive Tfh differentiation. These signals provided by both TCR and co-receptors during Tfh differentiation alter proliferation, survival, metabolism, cytokine production and transcription factor expression. This review will discuss how engagement of TCR and co-receptors work together to shape the formation and function of Tfh cells.

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“…They developed mice that bear a genetic tag allowing for AP-MS analysis of the RLTPR interactome in primary T cells, showed that RLTPR acts as a scaffold, bridging CD28 to the CARD11/CARMA1 cytosolic adaptor and to the NF-κB signaling pathway, and identified previously unknown proteins in the CD28 signaling pathway [100].…”

Section: Cluster Of Differentiation 28 (Cd28) Is a Protein Expressed mentioning

confidence: 99%

Mass spectrometry-based proteomic exploration of the human immune system: focus on the inflammasome, global protein secretion, and T cells

Nyman

Lorey

Cypryk

et al. 2017

Expert Review of Proteomics

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The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells

Cited by 70 publications

References 55 publications

Phosphoinositide 3‐kinase δ is a regulatory T‐cell target in cancer immunotherapy

Phosphoinositide 3‐kinase δ is a regulatory T‐cell target in cancer immunotherapy

Signals that drive T follicular helper cell formation

Mass spectrometry-based proteomic exploration of the human immune system: focus on the inflammasome, global protein secretion, and T cells

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