T cells (green) attaching to antigen presenting cells (red) resulting in formation of cytosolic protein clusters (yellow) that induce T cell activation.
Investigating lymphocyte activation is a critical aspect of immunological research that aims to understand the intricate mechanisms governing the immune response. Researchers investigate the process of lymphocyte activation to unravel the molecular pathways, receptors, and signaling cascades involved in triggering an immune response. By studying how lymphocytes are activated, we can gain insights into how the immune system combats cancer and develop better cancer-targeting therapies.
Lymphocytes such as T cells are key component of the immune system and play a pivotal role in recognizing and killing cancer cells. T cells express the T cell receptor (TCR) on the cell surface. TCR binding to an antigen presented by antigen presenting cells (APCs) leads to a signaling cascade that ends of activation of transcription factor NF-kB. We use imaging and biochemical tools to discover the mechanism of TCR signaling to NF-kB.
TCR signaling triggers the activation of various intracellular kinases, leading to the recruitment and activation signaling proteins such as PKC, CARMA1, BCL10, MALT1. The BCL10-MALT1 signaling complex activates another set of kinases called IKK which ultimately signals to NF-kB. NF-kB. NF-kB is a transcription factor that, which translocates to the cell nucleus and induce the expression of genes involved in T cell proliferation, cytokine production, and effector function.
The TCR to NF-kB pathway is a complex and tightly regulated process, ensuring that T cell activation occurs only when warranted and that the immune response is appropriately tailored to the specific antigen encountered. Dysregulation of this pathway can lead to immune-related disorders, autoimmune diseases, or impaired immune responses to infections and cancers. Understanding the intricacies of this pathway has significant implications for the development of immunotherapies and treatments aimed at modulating T cell responses in various disease contexts.
Read about our work on lymphocyte biology:
A transient, HDAC6-independent aggresome-like structure sustains T cell receptor-dependent Malt1 signal transduction
manuscript in review, 2023
Cellular Immunology, 2020
Methods in Molecular Biology, 2017
Methods in Molecular Biology, 2015
Science Signaling, 2014
Trends in Immunology, 2013
The Journal of Immunology, 2010