Understanding T cell signaling using membrane reconstitution

• Published in: Immunological reviews Vol. 291; no. 1; pp. 44 - 56
• Main Author: Hui, Enfu
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-09-2019
• Subjects: Animals; Antigen-presenting cells; Antigens; Biomarkers; Cascades; Cell activation; Cell Communication; Cell Membrane - chemistry; Cell Membrane - immunology; Cell Membrane - metabolism; Crosstalk; Extracellular Space; geometry; Humans; Immune response; Immune system; Ligands; Lipids; Lymphocyte Activation; Lymphocytes; Lymphocytes T; membrane; Membrane Proteins - metabolism; Membranes; Protein Binding; Protein interaction; Protein-Tyrosine Kinases - metabolism; Proteins; Receptors; Receptors, Antigen, T-Cell - metabolism; Receptors, Cell Surface - metabolism; reconstitution; Regulators; Signal Transduction; Signaling; T cell; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Viruses; reconstitution; geometry; membrane; signaling; T cell
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/imr.12767

Summary
T cells are central players of our immune system, as their functions range from killing tumorous and virus‐infected cells to orchestrating the entire immune response. In order for T cells to divide and execute their functions, they must be activated by antigen‐presenting cells (APCs) through a cell‐cell junction. Extracellular interactions between receptors on T cells and their ligands on APCs trigger signaling cascades comprised of protein‐protein interactions, enzymatic reactions, and spatial reorganization events, to either stimulate or repress T cell activation. Plasma membrane is the major platform for T cell signaling. Recruitment of cytosolic proteins to membrane‐bound receptors is a common critical step in many signaling pathways. Membranes decrease the dimensionality of protein‐protein interactions to enable weak yet biologically important interactions. Membrane resident proteins can phase separate into micro‐islands that promote signaling by enriching or excluding signal regulators. Moreover, some membrane lipids can either mediate or regulate cell signaling by interacting with signaling proteins. While it is critical to investigate T cell signaling in a cellular environment, the large number of signaling pathways involved and potential crosstalk have made it difficult to obtain precise, quantitative information on T cell signaling. Reconstitution of purified proteins to model membranes provides a complementary avenue for T cell signaling research. Here, I review recent progress in studying T cell signaling using membrane reconstitution approaches.