A5032885993- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Immunodeficiency and Autoimmune Disorders
- Galectins and Cancer Biology
- Caveolin-1 and cellular processes
- Chronic Myeloid Leukemia Treatments
- Cell Adhesion Molecules Research
- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Erythrocyte Function and Pathophysiology
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Nanofluid Flow and Heat Transfer
- Kruppel-like factors research
- Chronic Lymphocytic Leukemia Research
- Signaling Pathways in Disease
University of Freiburg
2014-2024
University Medical Center Freiburg
2018-2023
Max Planck Society
2014
Oncogenic JAK mutation sensitizes myeloproliferative neoplasms to immune checkpoint inhibition.
Activation of the T cell receptor (TCR) by antigen is key step in adaptive immunity.In abTCR, induces a conformational change at CD3 subunits (CD3 CC) that absolutely required for abTCR activation.Here, we demonstrate CC not induced stimulation mouse G8 or human Vg9Vd2 gdTCR.We find there fundamental difference between activation mechanisms and gdTCR map to constant regions TCRab/gd heterodimers.Enforced induction with less commonly used monoclonal anti-CD3 promoted proximal signaling but...
Lymphocyte-specific protein tyrosine kinase (LCK) is essential for T cell antigen receptor (TCR)–mediated signal transduction. Here, we report two siblings homozygous a novel LCK variant (c.1318C>T; P440S) characterized by lymphopenia with skewed memory phenotype, infant-onset recurrent infections, failure to thrive, and protracted diarrhea. The patients’ cells show residual TCR transduction proliferation following anti-CD3/CD28 phytohemagglutinin (PHA) stimulation. We demonstrate in...
Ligand binding to the TCR causes a conformational change at CD3 subunits expose CD3ε cytoplasmic proline-rich sequence (PRS). It was suggested that PRS is important for signaling and T cell activation. has been shown purified, recombinant SH3.1 domain of adaptor molecule noncatalytic region tyrosine kinase (Nck) can bind exposed CD3ε, but molecular mechanism how full-length Nck binds in cells not investigated so far. Using situ proximity ligation assay copurifications, we show requires...
T lymphocytes expressing the γδ cell receptor (γδ TCR) can recognize antigens expressed by tumor cells and subsequently kill these cells. are indeed used in cancer immunotherapy clinical trials. The anti-CD3ε antibody UCHT1 enhanced vitro killing activity of human an unknown molecular mechanism. Here, we demonstrate that Fab fragments UCHT1, which only bind monovalently to TCR, also expanded Vγ9Vδ2 or pan-γδ peripheral blood. induced Nck recruitment suggesting they stabilized TCR active CD3ε...
Introduction Antigen binding to the T cell antigen receptor (TCR) leads phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) CD3 complex, and thereby activation. The CD3ε subunit plays a unique role in TCR by recruiting kinase LCK adaptor protein NCK prior ITAM phosphorylation. Here, we aimed investigate how individual tyrosines impacts signalosome. Methods We mimicked irreversible tyrosine substituting glutamic acid for residues ITAM. Results Integrating...
The T cell antigen receptor (TCR) is expressed on cells, which orchestrate adaptive immune responses. It composed of the ligand-binding clonotypic TCRαβ heterodimer and non-covalently bound invariant signal-transducing CD3 complex. Among subunits, CD3ε cytoplasmic tail contains binding motifs for Src family kinase, Lck, adaptor protein, Nck. Lck binds to a kinase (RK) motif Nck proline-rich sequence (PRS). Both only become accessible upon ligand TCR facilitate recruitment independently...
Mutations affecting T-cell receptor (TCR) signaling typically cause combined immunodeficiency (CID) due to varying degrees of disturbed homeostasis and differentiation. Here, we describe two cousins with CID a novel nonsense mutation in LCK investigate the effect this on TCR signaling, function, Patients underwent clinical, genetic, immunological investigations. The was addressed primary cells LCK-deficient lines after expression mutated LCK. RESULTS: Both patients primarily presented...