A5013331073- T-cell and B-cell Immunology
- Cellular Mechanics and Interactions
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Force Microscopy Techniques and Applications
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Invertebrate Immune Response Mechanisms
- Erythrocyte Function and Pathophysiology
- Analytical Chemistry and Sensors
- Advanced Fluorescence Microscopy Techniques
- Receptor Mechanisms and Signaling
- Immune Response and Inflammation
- Cell Image Analysis Techniques
- Platelet Disorders and Treatments
- Lipid Membrane Structure and Behavior
- Single-cell and spatial transcriptomics
Georgia Institute of Technology
2016-2024
The Wallace H. Coulter Department of Biomedical Engineering
2016-2024
Parker Hannifin (United States)
2022-2024
Abstract Despite the clinical success of blocking its interactions, how PD-1 inhibits T-cell activation is incompletely understood, as exemplified by potency far exceeding what might be predicted from affinity for ligand-1 (PD-L1). This may partially attributed to PD-1’s targeting proximal signaling receptor (TCR) and co-stimulatory CD28 via activating Src homology region 2 domain-containing phosphatases (SHPs). Here, we report regulates initial TCR antigen recognition manifested in a...
The TCR integrates forces in its triggering process upon interaction with pMHC. Force elicits catch-slip bonds strong pMHCs but slip-only weak pMHCs. We develop two models and apply them to analyze 55 datasets, demonstrating the models' ability quantitatively integrate classify a broad range of bond behaviors biological activities. Comparing generic two-state model, our can distinguish class I from II MHCs correlate their structural parameters TCR/pMHC's potency trigger T cell activation....
Abstract Imaging flow cytometry (IFC) combines and fluorescence microscopy to enable high-throughput, multiparametric single-cell analysis with rich spatial details. However, current IFC techniques remain limited in their ability reveal subcellular information a high 3D resolution, throughput, sensitivity, instrumental simplicity. In this study, we introduce light-field cytometer (LFC), an system capable of high-content, single-shot, multi-color acquisition up 5,750 cells per second...
Abstract Antigen recognition by the T cell receptor (TCR) of CD4 + cells can be greatly enhanced coreceptor CD4. Yet, understanding molecular mechanism is hindered ultra-low affinity binding to class-II peptide-major histocompatibility complexes (pMHC). Here we show, using two-dimensional (2D) mechanical-based assays, that CD4–pMHC interaction 3-4 logs lower than cognate TCR–pMHC interactions, and it more susceptible increased dissociation forces (slip bond). In contrast, binds TCR-pre-bound...
Conventional approaches for studying receptor-mediated cell signaling, such as the western blot and flow cytometry, are limited in three aspects: 1) The perturbing preparation procedures often alter molecules from their native state on cell; 2) Long processing time before final readout makes it difficult to capture transient signaling events (<1 min); 3) experimental environments force-free, therefore unable visualize mechanical signals real time. In contrast these methods biochemistry...
A new biosensor was engineered to visualize Lck kinase preactivation and regulation in live T cells.
Programmed cell death-1 (PD-1) is an inhibitory receptor with essential role in maintaining peripheral tolerance and among the most promising immunotherapeutic targets for treating cancer, autoimmunity, infectious diseases. A complete understanding of consequences PD-1 engagement by its ligands, PD-L1 PD-L2, binding to B7-1 requires quantitative analysis their interactions at surface. We present here first situ kinetic PD-1/PD-ligands/B7-1 system. Consistent previous solution measurements,...
Force plays critical roles in cell adhesion and mechano-signaling, partially by regulating the dissociation rate, i.e., off-rate, of receptor-ligand bonds. However, mechanism such regulation still remains elusive. As a controversial topic field, when measuring "off-rate vs. force" relation same molecular system, different dynamic force spectroscopy (DFS) assays (namely, force-clamp force-ramp assays) often yield contradictive results. Such discrepancies hurdled our further understanding...
ABSTRACT Selectins and integrins are key players in the adhesion signaling cascade that recruits leukocytes to inflamed tissues. Selectin binding induces β2 integrin slow leukocyte rolling. Here, a micropipette was used characterize neutrophil E-selectin intercellular molecule-1 (ICAM-1) at room temperature. The time-dependent frequency displayed two-stage kinetics, with an E-selectin-mediated fast increase low plateau followed by high mediated intermediate-affinity of αLβ2 ICAM-1....
ABSTRACT Central to T cell biology, the receptor (TCR) integrates forces in its triggering process upon interaction with peptide-major histocompatibility complex (pMHC) 1-3 . Phenotypically, elicit TCR catch-slip bonds strong pMHCs but slip-only weak 4-10 While such correlation is commonly observed, quantitative bond pattern and degree of “catchiness” vary. We developed two models based on structure, elastic properties, force-induced conformational changes TCR–pMHC-I/II complexes derive from...
Immune checkpoint blockade targeting PD-1 shows great success in cancer therapy. However, the mechanism of how ligand binding initiates signaling remains unclear. As prognosis markers multiple cancers, soluble PD-L1 is found patient sera and can bind PD-1, but fails to suppress T cell function. This our previous observations that cells exert endogenous forces on PD-1-PD-L2 bonds prompt hypothesis mechanical force might be critical triggering, which missing case due lack support afforded by...
Abstract Antigen recognition of CD4+ T cells by the cell receptor (TCR) can be greatly enhanced coreceptor CD4. Yet, understanding molecular mechanism is hindered ultra-low affinity CD4 binding to class-II peptide-major histocompatibility complexes (pMHC). Using two-dimensional (2D) mechanical-based assays, we determined a CD4–pMHC interaction have 3-4 logs lower than cognate TCR–pMHC interactions, and susceptible increased dissociation forces (slip bond). In contrast, binds TCR-prebound...
Abstract Antigen recognition of CD4 + T cells by the cell receptor (TCR) can be greatly enhanced coreceptor 1–7 . Yet, understanding molecular mechanism is hindered ultra-low affinity binding to class-II peptide-major histocompatibility complexes (pMHC) 1,7–10 Using two-dimensional (2D) mechanical-based assays, we determined a CD4–pMHC interaction have 3-4 logs lower than cognate TCR–pMHC interactions 8 , and susceptible increased dissociation forces (slip bond) 5,8,11 In contrast, binds...
Abstract Central to T cell biology, the receptor (TCR) integrates forces in its triggering process upon interaction with peptide-major histocompatibility complex (pMHC). Phenotypically, elicit TCR catch-slip bonds strong pMHCs but slip-only weak pMHCs. While such correlation is generally observed, quantitative bond pattern and degree of “catchiness” vary. We developed two models based on structure, elastic properties, force-induced conformational changes TCR–pMHC-I/II complexes derive from...
Abstract CD8 + T cells underpin effective anti-tumor immune responses in melanoma; however, their functions are attenuated due to various immunosuppressive factors the tumor microenvironment (TME), resulting disease progression. cell function is elicited by receptor (TCR), which recognizes antigen peptide-major histocompatibility complex (pMHC) expressed on via direct physical contact, i.e., two-dimensional (2D) interaction. TCR–pMHC 2D affinity plays a central role recognition and...