A5031874114- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Blood disorders and treatments
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Peptidase Inhibition and Analysis
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
Technion – Israel Institute of Technology
2017-2025
The T cell receptor (TCR) signaling pathway is an ensemble of numerous proteins that are crucial for adequate immune response. Disruption any protein involved in this leads to severe immunodeficiency and unfavorable clinical outcomes. Here, we describe infant with who was found have novel biallelic mutations SLP76. SLP76 a key TCR other hematopoietic pathways. Previous studies were performed using Jurkat-derived human leukemic lines SLP76-deficient mice. Our current study links gene, the...
Thymocyte β-selection and positive-selection depend on TCR signaling via the immune adaptors SLP-76 LAT. Gads bridges recruitment of to LAT, yet is not required for maturation single positive (SP) thymocytes. To illuminate this paradox, we performed tamoxifen-induced ablation (GadsiKO), accompanied by expression tdTomato, compared development Gads-expressing (Tom-) Gads-ablated (Tom+) thymocytes within same mouse. GadsiKO exhibited impaired β- positive-selection, δ-selection was affected....
Constitutive dimerization of an adaptor molecule enables it to selectively amplify signaling by binding cooperatively complexes downstream antigen receptors.
The costimulatory receptor CD28 synergizes with the TCR to promote IL-2 production, cell survival, and proliferation; yet obligatory interdependence of signaling is not well understood. Upon stimulation, Gads, a Grb2-family adaptor, bridges interaction two additional adaptors, LAT SLP-76, form TCR-induced effector complex. SLP-76 binds Tec-family tyrosine kinase, Itk, which phosphorylates Y173 PLC-γ1 Y783. In this study, we identified TCR-inducible, Itk-mediated phosphorylation Gads Y45 in...
<h3>Background</h3> The interaction between the CD28 receptor and its B7 ligands has a crucial role in induction of potent persistent anti-tumor T cell response. Moreover, studies have implicated that efficient anti-PD1 therapy relies specifically on intact CD28/B7 signaling. We previously shown membranal is actively shed by MMP-2 MMP-13 upon stimulation human cancers, soluble can counteract cells maturation effector activity. Using several ex-vivo in-vivo methodologies, CD28-shedding was...
Abstract Gads is an immune adaptor that bridges the TCR-inducible interaction of two additional adaptors: SLP-76 and LAT. Thymic development profoundly impaired in absence or LAT, but moderately Gads-deficient mice, which accumulate non-naïve (CD44 + ) peripheral T cells. To better distinguish Gads-dependent -independent developmental transitions, we performed tamoxifen-induced ablation (Gads iKO ), accompanied by expression tdTomato, compared co-development Gads-expressing (Tom - -ablated...
Abstract Thymocyte development is tightly regulated by TCR signaling. Gads bridges a TCR-inducible interaction between SLP-76 and LAT, two adaptors that are essential for T cell development. In contrast, Gads-deficient mice have moderately impaired thymic accumulate non-naive peripheral cells of unclear origin. To illuminate the regulatory roles Gads, we developed model tamoxifen-induced ablation (Gads iKO), accompanied expression tdTomato. Using this model, followed fate iKO(Tom +) +(Tom −)...
Abstract The costimulatory receptor, CD28, synergizes with the T cell antigen receptor (TCR) to promote IL-2 production, survival and proliferation. Despite their profound synergy, obligatory interdependence of signaling pathways initiated by these two receptors is not well understood. Upon TCR stimulation, Gads, a Grb2-family adaptor, bridges interaction additional adaptors, LAT SLP-76, form TCR-induced effector complex. SLP-76 binds Tec-family tyrosine kinase, Itk, which phosphorylates at...