Regulation of Lck activity by CD4 and CD28 in the immunological synapse

Amy D. Holdorf; Kyeong Hee Lee; W. Richard Burack; Paul M. Allen; Andrey S. Shaw

doi:10.1038/ni761

Regulation of Lck activity by CD4 and CD28 in the immunological synapse

Amy D. Holdorf, Kyeong Hee Lee, W. Richard Burack, Paul M. Allen, Andrey S. Shaw

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185 Scopus citations

Abstract

Although the Src family tyrosine kinase Lck is essential for T cell receptor (TCR) signaling, whether or how Lck is activated is unknown. Using a phosphospecific antiserum to Lck, we show here that Lck becomes autophosphorylated when T cells are stimulated by antigen-presenting cells (APCs). We found that TCR cross-linking alone could not stimulate Lck autophosphorylation and CD45 was not required for this process. Instead, the T cell accessory molecules CD4 and CD28 cooperated to induce autophosphorylation of Lck. CD4 recruited Lck to the T cell-APC interface, whereas CD28 sustained Lck activation. These data show how the multiple interactions afforded by the immunological synapse drive efficient and highly specific signaling.

Original language	English
Pages (from-to)	259-264
Number of pages	6
Journal	Nature immunology
Volume	3
Issue number	3
DOIs	https://doi.org/10.1038/ni761
State	Published - 2002

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title = "Regulation of Lck activity by CD4 and CD28 in the immunological synapse",

abstract = "Although the Src family tyrosine kinase Lck is essential for T cell receptor (TCR) signaling, whether or how Lck is activated is unknown. Using a phosphospecific antiserum to Lck, we show here that Lck becomes autophosphorylated when T cells are stimulated by antigen-presenting cells (APCs). We found that TCR cross-linking alone could not stimulate Lck autophosphorylation and CD45 was not required for this process. Instead, the T cell accessory molecules CD4 and CD28 cooperated to induce autophosphorylation of Lck. CD4 recruited Lck to the T cell-APC interface, whereas CD28 sustained Lck activation. These data show how the multiple interactions afforded by the immunological synapse drive efficient and highly specific signaling.",

author = "Holdorf, {Amy D.} and Lee, {Kyeong Hee} and Burack, {W. Richard} and Allen, {Paul M.} and Shaw, {Andrey S.}",

note = "Funding Information: Acknowledgments We thank A. Chan, E. Unanue and J. Kim for critical review of the manuscript; S. Ranganath and D. Donermeyer for assistance with the T cell cultures; and J. Green for the CD28-deficient DO11.10 mice. Supported by the NIH (A. S.), the Cancer Research Institute (A. H.) and the Burroughs-Wellcome Fund (W. R. B.).",

year = "2002",

doi = "10.1038/ni761",

language = "English",

volume = "3",

pages = "259--264",

journal = "Nature immunology",

issn = "1529-2908",

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TY - JOUR

T1 - Regulation of Lck activity by CD4 and CD28 in the immunological synapse

AU - Holdorf, Amy D.

AU - Lee, Kyeong Hee

AU - Burack, W. Richard

AU - Allen, Paul M.

AU - Shaw, Andrey S.

N1 - Funding Information: Acknowledgments We thank A. Chan, E. Unanue and J. Kim for critical review of the manuscript; S. Ranganath and D. Donermeyer for assistance with the T cell cultures; and J. Green for the CD28-deficient DO11.10 mice. Supported by the NIH (A. S.), the Cancer Research Institute (A. H.) and the Burroughs-Wellcome Fund (W. R. B.).

PY - 2002

Y1 - 2002

N2 - Although the Src family tyrosine kinase Lck is essential for T cell receptor (TCR) signaling, whether or how Lck is activated is unknown. Using a phosphospecific antiserum to Lck, we show here that Lck becomes autophosphorylated when T cells are stimulated by antigen-presenting cells (APCs). We found that TCR cross-linking alone could not stimulate Lck autophosphorylation and CD45 was not required for this process. Instead, the T cell accessory molecules CD4 and CD28 cooperated to induce autophosphorylation of Lck. CD4 recruited Lck to the T cell-APC interface, whereas CD28 sustained Lck activation. These data show how the multiple interactions afforded by the immunological synapse drive efficient and highly specific signaling.

AB - Although the Src family tyrosine kinase Lck is essential for T cell receptor (TCR) signaling, whether or how Lck is activated is unknown. Using a phosphospecific antiserum to Lck, we show here that Lck becomes autophosphorylated when T cells are stimulated by antigen-presenting cells (APCs). We found that TCR cross-linking alone could not stimulate Lck autophosphorylation and CD45 was not required for this process. Instead, the T cell accessory molecules CD4 and CD28 cooperated to induce autophosphorylation of Lck. CD4 recruited Lck to the T cell-APC interface, whereas CD28 sustained Lck activation. These data show how the multiple interactions afforded by the immunological synapse drive efficient and highly specific signaling.

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DO - 10.1038/ni761

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VL - 3

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JO - Nature immunology

JF - Nature immunology

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ER -

Regulation of Lck activity by CD4 and CD28 in the immunological synapse

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