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Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):E5916-E5924. Epub 2016 Sep 19.

Three-dimensional localization of T-cell receptors in relation to microvilli using a combination of superresolution microscopies.

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Department of Chemical Physics, Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Anatomy, Kansai University of Health Sciences, Kumatori, Osaka 590-0482, Japan.
Institute for Academic Initiatives, Osaka University, Suita, Osaka 565-0871, Japan; MediCity Research Laboratory, University of Turku, FI-20521, Turku, Finland.
Department of Chemical Physics, Weizmann Institute of Science, Rehovot 76100, Israel;


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.


T-cell receptor; membrane protein clusters; microvilli; superresolution microscopy; total internal reflection microscopy

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