Membrane ultrastructure and T cell activation
- 1Sir William Dunn School of Pathology, University of Oxford, United Kingdom
The immune system serves as a crucial line of defense from infection and cancer, while also contributing to tissue homeostasis. Communication between immune cells is mediated by small soluble factors called cytokines, and also by direct cellular interactions. Cell-cell interactions are particularly important for T cell activation. T cells direct the adaptive immune response and therefore need to distinguish between self and foreign antigens. Even though decades have passed since the discovery of T cells, exactly why and how they are able to recognize and discriminate between antigens is still not fully understood. Early imaging of T cells was very successful in capturing the early stages of conjugate formation of T cells with antigen-presenting cells upon recognition of peptide-loaded major histocompatibility complexes by the T cell receptor (TCR). These studies lead to the discovery of a ‘supramolecular activation cluster’ now known as the immunological synapse, followed by the identification of microclusters of TCRs formed upon receptor triggering, that eventually coalesce at the center of the synapse. New developments in light microscopy have since allowed attention to turn to the very earliest stages of T cell activation, and to resting cells, at high resolution. This includes single molecule localization microscopy, which has been applied to the question of whether TCRs are pre-clustered on resting T cells, and lattice-light sheet microscopy that has enabled imaging of whole cells interacting with antigen-presenting cells. The utilization of lattice-light sheet microscopy has yielded important insights into structures called microvilli, which are small membrane protrusions on T cells that seem likely to have a large impact on T cell recognition and activation. Here we consider how imaging has shaped our thinking about T cell activation. We summarize recent findings obtained by applying more advanced microscopy techniques and discuss some of the limitations of these methods.
Keywords: T cell signaling, Microvilli, invadosome-like protrusions, membrane topology, Microscopy, microclusters, Immunological Synapse
Received: 13 Jun 2018;
Accepted: 31 Aug 2018.
Edited by:Jorge Bernardino De La Serna, United Kingdom Research and Innovation, United Kingdom
Reviewed by:Christoph Wülfing, University of Bristol, United Kingdom
Marek Cebecauer, J. Heyrovsky Institute of Physical Chemistry (ASCR), Czechia
Copyright: © 2018 Pettmann, Santos, Dushek and Davis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Prof. Omer Dushek, University of Oxford, Sir William Dunn School of Pathology, Oxford, OX1 3RE, United Kingdom, email@example.com
Dr. Simon J. Davis, University of Oxford, Sir William Dunn School of Pathology, Oxford, OX1 3RE, United Kingdom, firstname.lastname@example.org