T cells must overcome a negatively charged, dense layer of polysaccharide chains of membrane proteins and lipids, the glycocalyx, to scan target cells during the early stages of T cell activation, and use cell projections, microvilli, to breach the glycocalyx. Using glass-supported bilayer mimics of the APC surface to study this interaction, Jenkins and Kröbel et al. found that antigen discrimination by T cells critically depended on the formation of small CD58:CD2-stabilized, microvillus-sized close contacts. Variations in CD2 expression levels changed T cell responsiveness, and when contact size increased, T cell ligand discrimination was impaired.
Contributed by Ute Burkhardt
ABSTRACT: T cells use finger-like protrusions called 'microvilli' to interrogate their targets, but why they do so is unknown. To form contacts, T cells must overcome the highly charged, barrier-like layer of large molecules forming a target cell's glycocalyx. Here, T cells are observed to use microvilli to breach a model glycocalyx barrier, forming numerous small (<0.5 m diameter) contacts each of which is stabilized by the small adhesive protein CD2 expressed by the T cell, and excludes large proteins including CD45, allowing sensitive, antigen dependent TCR signaling. In the absence of the glycocalyx or when microvillar contact-size is increased by enhancing CD2 expression, strong signaling occurs that is no longer antigen dependent. Our observations suggest that, modulated by the opposing effects of the target cell glycocalyx and small adhesive proteins, the use of microvilli equips T cells with the ability to effect discriminatory receptor signaling.
Author Info: (1) Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. Medical Research Council Human Immunology Unit, John Radcliffe Hospital, U
Author Info: (1) Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. (2) Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. (3) Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. (4) Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. (5) Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. (6) Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. (7) Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. (8) Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. (9) Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. (10) Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. (11) Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. (12) Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. simon.davis@imm.ox.ac.uk. Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. simon.davis@imm.ox.ac.uk. (13) Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. dk10012@cam.ac.uk.
