title: Three-dimensional localization of T-cell receptors in relation to microvilli using a combination of superresolution microscopies.
abstract: Leukocyte microvilli are flexible projections enriched with adhesion molecules. The role of these cellular projections in the ability of T cells to probe antigen-presenting cells has been elusive. In this study, we probe the spatial relation of microvilli and T-cell receptors (TCRs), the major molecules responsible for antigen recognition on the T-cell membrane. To this end, an effective and robust methodology for mapping membrane protein distribution in relation to the 3D surface structure of cells is introduced, based on two complementary superresolution microscopies. Strikingly, TCRs are found to be highly localized on microvilli, in both peripheral blood human T cells and differentiated effector T cells, and are barely found on the cell body. This is a decisive demonstration that different types of T cells universally localize their TCRs to microvilli, immediately pointing to these surface projections as effective sensors for antigenic moieties. This finding also suggests how previously reported membrane clusters might form, with microvilli serving as anchors for specific T-cell surface molecules.
authors.affiliation: Department of Chemical Physics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yunmin
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Department of Chemical Physics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Riven
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Sara W
authors.initials: SW
authors.lastname: Feigelson
authors.affiliation: Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Kartvelishvily
authors.affiliation: Department of Anatomy, Kansai University of Health Sciences, Kumatori, Osaka 590-0482, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tohya
authors.affiliation: Institute for Academic Initiatives, Osaka University, Suita, Osaka 565-0871, Japan; MediCity Research Laboratory, University of Turku, FI-20521, Turku, Finland.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Alon
authors.affiliation: Department of Chemical Physics, Weizmann Institute of Science, Rehovot 76100, Israel; Gilad.haran@weizmann.ac.il.
authors.forename: Gilad
authors.initials: G
authors.lastname: Haran
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D021621:Imaging, Three-Dimensional; D019041:L-Selectin / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008853:Microscopy / Q000379:methods*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D053778:Thiazolidines; D019041:L-Selectin; C037067:latrunculin A
keywords: T-cell receptor; membrane protein clusters; microvilli; superresolution microscopy; total internal reflection microscopy