title: Proximity of TCR and its CD8 coreceptor controls sensitivity of T cells.
abstract: Spatial organisation of T cell receptor (TCR) and its coreceptor CD8 on the surface of live naïve and Ag-experienced CD8(+) T cells was resolved by fluorescence lifetime cross-correlation microscopy. We found that exposure of naïve CD8(+) T cells to antigen (Ag) causes formation of [TCR, CD8] functional ensembles on the cell surface which correlated with significantly enhanced sensitivity of these cells. In contrast, TCR and CD8 are randomly distributed on the surface of naïve cells. Our model suggests that close proximity of TCR and CD8 can increase Ag sensitivity of T cells by significant accelerating the TCR-peptide-major histocompatibility complex (pMHC) binding rate and stabilisation of this complex. We suggest that the proximity of these primary signalling molecules contributes to the mechanism of functional avidity maturation of CD8(+) T cells by switching them from a low to high sensitivity mode.
authors.affiliation: Institute of Immunology and Infection Research, The University of Edinburgh, Edinburgh EH9 3JT, UK.
authors.forename: Jessica G
authors.initials: JG
authors.lastname: Borger
authors.affiliation: Institute of Immunology and Infection Research, The University of Edinburgh, Edinburgh EH9 3JT, UK.
authors.forename: Rose
authors.initials: R
authors.lastname: Zamoyska
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS Scotland, UK; Collaborative Optical Spectroscopy, Micromanipulation and Imaging Centre COSMIC, School of Physics and Astronomy, The University of Edinburgh, Mayfield Road, Edinburgh EH9 3JZ, UK. Electronic address: D.Gakamsky@hw.ac.uk.
authors.forename: Dmitry M
authors.initials: DM
authors.lastname: Gakamsky
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D000099192:CD69 Antigens
chemical_list: D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens
keywords: APC; Ag; Antigen recognition; CD8 coreceptor; CTL; EM; FCS; Fluorescence lifetime cross-correlation microscopy; Functional avidity maturation; LN; NSOM; T cell receptor; T cell receptor signalling; T cell sensitivity; TCR; antigen; antigen presenting cell; cytotoxic T cell lymphocyte; electron microscopy; fetal calf serum; lymph node; mAb; monoclonal antibody; near-field scanning optical microscopy