A5023305368- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Signaling Pathways in Disease
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Single-cell and spatial transcriptomics
- Neonatal Respiratory Health Research
- Ubiquitin and proteasome pathways
- 14-3-3 protein interactions
- Immune Response and Inflammation
- Ion Transport and Channel Regulation
- Cancer Immunotherapy and Biomarkers
- NF-κB Signaling Pathways
- Mycobacterium research and diagnosis
- Mosquito-borne diseases and control
- Erythrocyte Function and Pathophysiology
- HIV Research and Treatment
- Cancer Cells and Metastasis
- Ion channel regulation and function
- 3D Printing in Biomedical Research
- Complement system in diseases
Institut Pasteur
2011-2024
Inserm
2016-2024
Université Paris Cité
2022-2024
La Ligue Contre le Cancer
2020-2024
Centre National de la Recherche Scientifique
2003-2017
Annamalai University
2011
Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes
2009
Centre National pour la Recherche Scientifique et Technique (CNRST)
2007
Center of Molecular Immunology (Cuba)
2005
Institut de Génétique Moléculaire de Montpellier
2004
Highlights•Single-molecule microscopy maps signaling molecules on the resting T cell membrane•TCRαβ, TCRζ, CD4, CD2, Lck, and LAT are all highly enriched microvilli•TCR localization is mediated by ERM proteins•Microvilli hubs for TCR signaling, facilitating fast initial immune responseSummaryT surfaces covered with microvilli, actin-rich flexible protrusions. We use super-resolution to show that ≥90% of receptor (TCR) complex TCRαβ as well co-receptor CD4 (cluster differentiation 4)...
Following T cell antigen receptor (TCR) engagement, the protein tyrosine kinase (PTK) ZAP-70 is rapidly phosphorylated on several residues, presumably by two mechanisms: an autophosphorylation and a trans-phosphorylation Src-family PTK Lck. These events have been implicated in both positive negative regulation of activity coupling this to downstream signaling pathways cells. We show here that Tyr315 Tyr319 interdomain B are autophosphorylated vitro become vivo upon TCR triggering. Moreover,...
T-cell antigen receptor-induced signaling requires both ZAP-70 and Lck protein-tyrosine kinases. One essential function of in this process is to phosphorylate up-regulate its catalytic activity. We have previously shown that after receptor stimulation, binds via Src homology 2 (SH2) domain (LckSH2) and, more recently, Tyr319 phosphorylated vivo plays a positive regulatory role. Here, we investigated the possibility mediates SH2-dependent interaction between ZAP-70. show phosphopeptide...
The SH2 domain–containing leukocyte protein of 76 kD (SLP-76) is a pivotal element the signaling machinery controlling T cell receptor (TCR)-mediated activation. Here, we identify 14-3-3ε and ζ proteins as SLP-76 binding partners. This interaction was induced by TCR ligation required phosphorylation at serine 376. Ribonucleic acid interference in vitro experiments showed that 376 target hematopoietic progenitor kinase 1 (HPK-1). Interestingly, either S376A mutation or HPK-1 knockdown...
Abstract Mycolactone is a diffusible lipid toxin produced by Mycobacterium ulcerans, the causative agent of necrotizing skin disease referred to as Buruli ulcer. Intriguingly, patients with progressive lesions display systemic suppression Th1 responses that resolves on surgical excision infected tissues. In this study, we examined effects mycolactone functional biology T cells and identified two mechanisms which suppresses cell responsiveness antigenic stimulation. At noncytotoxic...
Mycolactone is a macrolide produced by Mycobacterium ulcerans with immunomodulatory properties. Here, we describe that in mouse, mycolactone injection led to massive T-cell depletion peripheral lymph nodes (PLNs) was associated defective expression of L-selectin (CD62-L). Importantly, preexposure impaired the capacity T cells reach PLNs after adoptive transfer, respond chemotactic signals, and expand upon antigenic stimulation vivo. We found mycolactone-induced suppression CD62-L human...
Antigen recognition within immunological synapses triggers and sustains T cell activation by nucleating protein microclusters that gather receptors (TCRs), kinases, adaptors. Dissipation of these results in signal termination, but how this process is regulated unclear. In paper, we reveal release the adaptors SLP76 GADS from signaling induced serine/threonine kinase HPK1 phosphorylation plays a major role process. We found was recruited into triggered their dissipation inducing...
Adenomatous polyposis coli (APC) is a tumor suppressor whose mutations underlie familial adenomatous (FAP) and colorectal cancer. Although its role in intestinal epithelial cells well characterized, APC importance T cell biology ill defined. regulates cytoskeleton organization, polarity, migration various types. Here, we address whether plays lymphocyte migration. Using series of tools, unveiled that from FAP patients carrying display impaired adhesion motility constrained environments. We...
Evaluating the ability of cytotoxic T lymphocytes (CTLs) to eliminate tumor cells is crucial, for instance, predict efficiency cell therapy in personalized medicine. However, destruction a by CTLs involves CTL migration extra-tumoral environment, accumulation on tumor, antigen recognition, and cooperation killing cancer cells. Therefore, identifying limiting steps this complex process requires spatio-temporal measurements different cellular events over long periods. Here, we use...
The product of the protooncogene Vav1 participates in multiple signaling pathways and is a critical regulator antigen–receptor B T lymphocytes, but its role during vivo natural killer (NK) cell differentiation not known. Here we have studied NK development Vav1−/− mice found that, contrast to NK-T cells, absolute numbers phenotypically mature cells were reduced. produced normal amounts interferon (IFN)-γ response Listeria monocytogenes controlled early infection showed reduced tumor...
Adenomatous polyposis coli (APC) is a polarity regulator and tumor suppressor associated with familial adenomatous colorectal cancer development. Although extensively studied in epithelial transformation, the effect of APC on T lymphocyte activation remains poorly defined. We found that ensures cell receptor-triggered through Nuclear Factor Activated cells (NFAT), since necessary for NFAT's nuclear localization microtubule-dependent fashion NFAT-driven transcription leading to cytokine gene...
In non-small cell lung carcinoma (NSCLC), stimulation of toll-like receptor 7 (TLR7), a for single stranded RNA, is linked to tumor progression and resistance anticancer chemotherapy. However, the mechanism this effect has been elusive. Here, using murine model adenocarcinoma, we demonstrate key role TLR7 expressed by malignant (rather than stromal immune) cells, in recruitment myeloid derived suppressor cells (MDSCs), induced after stimulation, resulting accelerated growth metastasis....
Protozoan pathogens secrete nanosized particles called extracellular vesicles (EVs) to facilitate their survival and chronic infection. Here, we show the inhibition by Plasmodium berghei NK65 blood stage-derived EVs of proliferative response CD4+ T cells in antigen presentation. Importantly, these results were confirmed vivo capacity diminish ovalbumin-specific delayed type hypersensitivity response. We identified two proteins associated with EVs, histamine releasing factor (HRF) elongation...
The protein-tyrosine kinase ZAP-70 is implicated, together with the Src p56(lck), in controlling early steps of T-cell antigen receptor (TCR) signaling cascade. To help elucidate further mechanism by which regulates these initial events, we used a dominant-negative mutant approach. We overexpressed Jurkat line mutated on Tyr-492 and Tyr-493 putative regulatory loop its domain. This inhibited TCR-induced activation nuclear factor activated T cells interfering both intracellular calcium...
Abstract The role of endosomes in receptor signal transduction is a long-standing question, which remains largely unanswered. T cell Ag and various components its proximal signaling machinery are associated with distinct endosomal compartments, but how traffic affects ill-defined. In this article, we demonstrate human cells that the subcellular localization function protein tyrosine kinase Lck depends on Rab11 effector FIP3 (Rab11 family interacting protein-3). overexpression or silencing...