Initiation of T cell signaling by CD45 segregation at 'close contacts'

Research output: Contribution to journalArticle

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Initiation of T cell signaling by CD45 segregation at 'close contacts'. / Chang, Veronica T; Fernandes, Ricardo A; Ganzinger, Kristina A; Lee, Steven F; Siebold, Christian; McColl, James; Jönsson, Peter; Palayret, Matthieu; Harlos, Karl; Coles, Charlotte H; Jones, E Yvonne; Lui, Yuan; Huang, Elizabeth; Gilbert, Robert J C; Klenerman, David; Aricescu, A Radu; Davis, Simon J.

In: Nature Immunology, Vol. 17, No. 5, 05.2016, p. 574-582.

Research output: Contribution to journalArticle

Harvard

Chang, VT, Fernandes, RA, Ganzinger, KA, Lee, SF, Siebold, C, McColl, J, Jönsson, P, Palayret, M, Harlos, K, Coles, CH, Jones, EY, Lui, Y, Huang, E, Gilbert, RJC, Klenerman, D, Aricescu, AR & Davis, SJ 2016, 'Initiation of T cell signaling by CD45 segregation at 'close contacts'', Nature Immunology, vol. 17, no. 5, pp. 574-582. https://doi.org/10.1038/ni.3392

APA

Chang, V. T., Fernandes, R. A., Ganzinger, K. A., Lee, S. F., Siebold, C., McColl, J., ... Davis, S. J. (2016). Initiation of T cell signaling by CD45 segregation at 'close contacts'. Nature Immunology, 17(5), 574-582. https://doi.org/10.1038/ni.3392

CBE

Chang VT, Fernandes RA, Ganzinger KA, Lee SF, Siebold C, McColl J, Jönsson P, Palayret M, Harlos K, Coles CH, Jones EY, Lui Y, Huang E, Gilbert RJC, Klenerman D, Aricescu AR, Davis SJ. 2016. Initiation of T cell signaling by CD45 segregation at 'close contacts'. Nature Immunology. 17(5):574-582. https://doi.org/10.1038/ni.3392

MLA

Vancouver

Chang VT, Fernandes RA, Ganzinger KA, Lee SF, Siebold C, McColl J et al. Initiation of T cell signaling by CD45 segregation at 'close contacts'. Nature Immunology. 2016 May;17(5):574-582. https://doi.org/10.1038/ni.3392

Author

Chang, Veronica T ; Fernandes, Ricardo A ; Ganzinger, Kristina A ; Lee, Steven F ; Siebold, Christian ; McColl, James ; Jönsson, Peter ; Palayret, Matthieu ; Harlos, Karl ; Coles, Charlotte H ; Jones, E Yvonne ; Lui, Yuan ; Huang, Elizabeth ; Gilbert, Robert J C ; Klenerman, David ; Aricescu, A Radu ; Davis, Simon J. / Initiation of T cell signaling by CD45 segregation at 'close contacts'. In: Nature Immunology. 2016 ; Vol. 17, No. 5. pp. 574-582.

RIS

TY - JOUR

T1 - Initiation of T cell signaling by CD45 segregation at 'close contacts'

AU - Chang, Veronica T

AU - Fernandes, Ricardo A

AU - Ganzinger, Kristina A

AU - Lee, Steven F

AU - Siebold, Christian

AU - McColl, James

AU - Jönsson, Peter

AU - Palayret, Matthieu

AU - Harlos, Karl

AU - Coles, Charlotte H

AU - Jones, E Yvonne

AU - Lui, Yuan

AU - Huang, Elizabeth

AU - Gilbert, Robert J C

AU - Klenerman, David

AU - Aricescu, A Radu

AU - Davis, Simon J

PY - 2016/5

Y1 - 2016/5

N2 - It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell antigen receptor (TCR) triggering, but how such segregation occurs and whether it can initiate signaling is unclear. Using structural and biophysical analysis, we show that the extracellular region of CD45 is rigid and extends beyond the distance spanned by TCR-ligand complexes, implying that sites of TCR-ligand engagement would sterically exclude CD45. We also show that the formation of 'close contacts', new structures characterized by spontaneous CD45 and kinase segregation at the submicron-scale, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the potent signaling effects of, local CD45 and kinase segregation. TCR ligands have the potential to heighten signaling simply by holding receptors in close contacts.

AB - It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell antigen receptor (TCR) triggering, but how such segregation occurs and whether it can initiate signaling is unclear. Using structural and biophysical analysis, we show that the extracellular region of CD45 is rigid and extends beyond the distance spanned by TCR-ligand complexes, implying that sites of TCR-ligand engagement would sterically exclude CD45. We also show that the formation of 'close contacts', new structures characterized by spontaneous CD45 and kinase segregation at the submicron-scale, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the potent signaling effects of, local CD45 and kinase segregation. TCR ligands have the potential to heighten signaling simply by holding receptors in close contacts.

KW - Crystallography, X-Ray

KW - HEK293 Cells

KW - Humans

KW - Jurkat Cells

KW - Leukocyte Common Antigens

KW - Lymphocyte Specific Protein Tyrosine Kinase p56(lck)

KW - Microscopy, Electron

KW - Microscopy, Fluorescence

KW - Models, Molecular

KW - Protein Structure, Tertiary

KW - Receptors, Antigen, T-Cell

KW - Signal Transduction

KW - T-Lymphocytes

KW - Time Factors

KW - ZAP-70 Protein-Tyrosine Kinase

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ni.3392

DO - 10.1038/ni.3392

M3 - Article

VL - 17

SP - 574

EP - 582

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 5

ER -