PhD student, Karolinska Institute
Using DNA as a tool to understand how immune cells communicate
One of the ways how cells communicate with each other is by 'feeling' patterns of proteins on the surfaces of neighbouring cells. Depending on the type of protein patterns, for example, the distance between proteins, this can influence the outcome of cell signalling. T cells are one of the important players in our body that provide defence and immunity against invading pathogens. They go around in our body sensing cells and checking for infections. Our team is trying to understand if certain protein patterns on healthy or infected cells may affect how T cells behave. Since these protein patterns are so small, we need a tool at the nanoscale level to recreate them in the lab.
Our team is using DNA decorated with protein patterns of known distances as a nano probe to test how different protein patterns affect how T cells behave and interact with other cells. This knowledge could give us more insight into T cell signalling and open doors to new T cell therapeutics.
Abstract: T cell receptor (TCR) activation and signaling precede immunological synapse formation and are sustained for hours after initiation. However, the precise physical sites of the initial and sustained TCR signaling are not definitively known. We report here that T cell activation was initiated and sustained in TCR-containing microclusters generated at the initial contact sites and the periphery of the mature immunological synapse. Microclusters containing TCRs, the tyrosine kinase Zap70 and the adaptor molecule SLP-76 were continuously generated at the periphery. TCR microclusters migrated toward the central supramolecular cluster, whereas Zap70 and SLP-76 dissociated from these microclusters before the microclusters coalesced with the TCR-rich central supramolecular cluster. Tyrosine phosphorylation and calcium influx were induced as microclusters formed at the initial contact sites. Inhibition of signaling prevented recruitment of Zap70 into the microclusters. These results indicated that TCR-rich microclusters initiate and sustain TCR signaling.
Pub.: 08 Nov '05, Pinned: 28 Aug '17
Abstract: Dendritic cells (DCs) are myeloid lineage cells that are imprinted by their environment and that mature in response to microbial products. A crucial role of the DC is to impart this context-specific information to T cells as well as to present self and foreign MHC-peptide complexes through formation of an immunological synapse. The structure of the T cell-DC immunological synapse departs from the canonical structure formed with B cells or with supported planar bilayers in that it has multiple foci of T-cell receptor interactions rather than a central focus. Recent studies on model systems provide insight into the mechanisms and biological consequences of the unique T cell-DC synaptic patterns.
Pub.: 17 Jun '06, Pinned: 28 Aug '17
Abstract: Classical alphabeta T cells protect the host by monitoring intracellular and extracellular proteins in a two-step process. The first step is protein degradation and combination with a major histocompatibility complex (MHC) molecule, leading to surface expression of this amalgam (antigen processing). The second step is the interaction of the T cell receptor with the MHC-peptide complex, leading to signaling in the T cells (antigen recognition). The context for this interaction is a T cell-antigen presenting cell junction, known as an immunological synapse if symmetric and stable and as a kinapse if asymmetric and mobile. The physiological recognition of a ligand takes place most efficiently in the F-actin-rich lamellipodium and is F-actin dependent in stages of formation and triggering and myosin II dependent for signal amplification. This review discusses how these concepts emerged from early studies on adhesion, signaling, and cell biology of T cells.
Pub.: 18 Apr '09, Pinned: 28 Aug '17