TCRs are randomly distributed on the plasma membrane of resting antigen-experienced T cells.

Nature Immunology
Benedikt RossbothGerhard J Schütz

Abstract

The main function of T cells is to identify harmful antigens as quickly and precisely as possible. Super-resolution microscopy data have indicated that global clustering of T cell antigen receptors (TCRs) occurs before T cell activation. Such pre-activation clustering has been interpreted as representing a potential regulatory mechanism that fine tunes the T cell response. We found here that apparent TCR nanoclustering could be attributed to overcounting artifacts inherent to single-molecule-localization microscopy. Using complementary super-resolution approaches and statistical image analysis, we found no indication of global nanoclustering of TCRs on antigen-experienced CD4+ T cells under non-activating conditions. We also used extensive simulations of super-resolution images to provide quantitative limits for the degree of randomness of the TCR distribution. Together our results suggest that the distribution of TCRs on the plasma membrane is optimized for fast recognition of antigen in the first phase of T cell activation.

References

Jul 1, 1983·Biophysical Journal·B Goldstein, F W Wiegel
Apr 20, 2002·Biophysical Journal·Russell E ThompsonWatt W Webb
Dec 4, 2003·Nature Reviews. Immunology·Johannes B Huppa, Mark M Davis
Aug 10, 2005·The Journal of Experimental Medicine·Wolfgang W A SchamelBalbino Alarcón
Aug 10, 2006·Nature Methods·Michael J RustXiaowei Zhuang
Aug 12, 2006·Science·Eric BetzigHarald F Hess
Sep 19, 2006·Biophysical Journal·Samuel T HessMichael D Mason
Dec 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Björn F LillemeierMark M Davis
Jul 8, 2008·Angewandte Chemie·Jan VogelsangPhilip Tinnefeld
Jul 19, 2008·Methods : a Companion to Methods in Enzymology·Stefan Wieser, Gerhard J Schütz
Jul 23, 2008·Angewandte Chemie·Mike HeilemannMarkus Sauer
Aug 19, 2009·Biophysical Journal·Maria A KiskowskiAnne K Kenworthy
Dec 24, 2010·Nature Reviews. Immunology·Lakshmi BalagopalanLawrence E Samelson
Jun 7, 2011·Nature Immunology·David J WilliamsonKatharina Gaus
Jun 15, 2011·Nature Methods·Paolo AnnibaleAleksandra Radenovic
Sep 20, 2011·Nature Methods·Prabuddha SenguptaJennifer Lippincott-Schwartz
Dec 4, 2012·Nature Immunology·Jérémie RossyKatharina Gaus
Dec 12, 2012·Journal of Biomedical Optics·Claire Robertson, Steven C George
Jan 3, 2013·Immunological Reviews·Wolfgang W A Schamel, Balbino Alarcón
Jan 26, 2013·Nature Protocols·Prabuddha SenguptaJennifer Lippincott-Schwartz
Apr 23, 2013·Biophysical Journal·Enrico Klotzsch, Gerhard J Schütz
Dec 3, 2014·Journal of Cell Science·Maria F Garcia-ParajoKen Jacobson
Mar 22, 2016·Nature Immunology·Veronica T ChangSimon J Davis
Jun 14, 2016·Nature Methods·Florian BaumgartGerhard J Schütz
Jun 16, 2016·Proceedings of the National Academy of Sciences of the United States of America·Ying S HuBjörn F Lillemeier
Aug 31, 2016·Proceedings of the National Academy of Sciences of the United States of America·Sophie V PageonKatharina Gaus
Sep 21, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yunmin JungGilad Haran
Sep 7, 2017·Nature Reviews. Molecular Cell Biology·Steffen J SahlStefan Jakobs
Feb 25, 2018·Nature Immunology·Ana Mafalda SantosSteven F Lee
Apr 18, 2018·Nature Immunology·Mario BrameshuberJohannes B Huppa

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Citations

Nov 10, 2018·Methods and Applications in Fluorescence·Florian BaumgartGerhard J Schütz
Nov 7, 2019·Proceedings of the National Academy of Sciences of the United States of America·Melissa BedardVincenzo Cerundolo
Jan 3, 2020·Physical Chemistry Chemical Physics : PCCP·Tina KošutaCarlo Manzo
Jan 7, 2020·Royal Society Open Science·Daniel J NievesKatharina Gaus
Apr 2, 2020·Annual Review of Analytical Chemistry·Fang LuoXiaohong Fang
Jul 19, 2020·The FEBS Journal·Pablo F CéspedesErdinc Sezgin
Oct 16, 2018·Frontiers in Immunology·Johannes PettmannSimon J Davis
Feb 20, 2019·Nature Communications·Maria Angela Gomes de CastroFelipe Opazo
Feb 13, 2019·Journal of Cell Science·Jesse GoyetteKatharina Gaus
Jul 29, 2019·The Journal of Membrane Biology·Laurent Limozin, Pierre-Henri Puech
Mar 7, 2020·Journal of Cell Science·Lai WenKlaus Ley
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Megan V FarrellJesse Goyette
Apr 26, 2019·Frontiers in Immunology·Laabiah WasimBebhinn Treanor
Apr 20, 2019·Frontiers in Immunology·Daniela Glatzová, Marek Cebecauer
Mar 8, 2020·Scientific Reports·Andreas M ArnoldGerhard J Schütz
Jan 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Joschka HellmeierEva Sevcsik
Nov 13, 2020·Frontiers in Cell and Developmental Biology·Alexander M MørchMichael L Dustin
Jan 26, 2021·Frontiers in Cell and Developmental Biology·Salma Pathan-ChhatbarWolfgang W Schamel
Mar 27, 2021·Frontiers in Immunology·Rachel E LamertonDylan M Owen
Apr 19, 2021·The International Journal of Biochemistry & Cell Biology·Johan HummertDirk-Peter Herten
Aug 19, 2021·Wiener klinische Wochenschrift
Oct 17, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ádám KeneseiGyörgy Vámosi

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Methods Mentioned

BETA
transgenic
fluorescence-microscopy
super-resolution microscopy
size-exclusion chromatography

Software Mentioned

Matlab
dSTORM
Labview
ImageJ
Matlab code

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