The immunological synapse and CD28-CD80 interactions

Shannon K. Bromley; Andrea Iaboni; Simon J. Davis; Adrian Whitty; Jonathan M. Green; Andrey S. Shaw; Arthur Weiss; Michael L. Dustin

doi:10.1038/ni737

The immunological synapse and CD28-CD80 interactions

Shannon K. Bromley, Andrea Iaboni, Simon J. Davis, Adrian Whitty, Jonathan M. Green, Andrey S. Shaw, Arthur Weiss, Michael L. Dustin

Division of Pulmonary & Critical Care Medicine

Research output: Contribution to journal › Article › peer-review

257 Scopus citations

Abstract

According to the two-signal model of T cell activation, costimulatory molecules augment T cell receptor (TCR) signaling, whereas adhesion molecules enhance TCR-MHC-peptide recognition. The structure and binding properties of CD28 imply that it may perform both functions, blurring the distinction between adhesion and costimulatory molecules. Our results show that CD28 on naïve T cells does not support adhesion and has little or no capacity for directly enhancing TCR-MHC-peptide interactions. Instead of being dependent on costimulatory signaling, we propose that a key function of the immunological synapse is to generate a cellular microenvironment that favors the interactions of potent secondary signaling molecules, such as CD28.

Original language	English
Pages (from-to)	1159-1166
Number of pages	8
Journal	Nature immunology
Volume	2
Issue number	12
DOIs	https://doi.org/10.1038/ni737
State	Published - 2001

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@article{a9a58078ac714ff38b6421dd8beef37b,

title = "The immunological synapse and CD28-CD80 interactions",

abstract = "According to the two-signal model of T cell activation, costimulatory molecules augment T cell receptor (TCR) signaling, whereas adhesion molecules enhance TCR-MHC-peptide recognition. The structure and binding properties of CD28 imply that it may perform both functions, blurring the distinction between adhesion and costimulatory molecules. Our results show that CD28 on na{\"i}ve T cells does not support adhesion and has little or no capacity for directly enhancing TCR-MHC-peptide interactions. Instead of being dependent on costimulatory signaling, we propose that a key function of the immunological synapse is to generate a cellular microenvironment that favors the interactions of potent secondary signaling molecules, such as CD28.",

author = "Bromley, {Shannon K.} and Andrea Iaboni and Davis, {Simon J.} and Adrian Whitty and Green, {Jonathan M.} and Shaw, {Andrey S.} and Arthur Weiss and Dustin, {Michael L.}",

note = "Funding Information: Acknowledgements We thank H. Reiser and M. Naquet for cells producing the 1610A1 and H155 antibodies, respectively; G. Freeman for the mCD80 cDNA;A. Holdorf for Jurkat cells expressing truncation mutants of murine CD28; R. Burack for sharing his unpublished results on cooperation of CD2 and CD28; R. Houdei for cell and antibody production; and R. Barrett for preparation of the manuscript. Supported by funds from the NIH, HHMI, the Whitaker Foundation and Irene Diamond.",

year = "2001",

doi = "10.1038/ni737",

language = "English",

volume = "2",

pages = "1159--1166",

journal = "Nature immunology",

issn = "1529-2908",

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T1 - The immunological synapse and CD28-CD80 interactions

AU - Bromley, Shannon K.

AU - Iaboni, Andrea

AU - Davis, Simon J.

AU - Whitty, Adrian

AU - Green, Jonathan M.

AU - Shaw, Andrey S.

AU - Weiss, Arthur

AU - Dustin, Michael L.

N1 - Funding Information: Acknowledgements We thank H. Reiser and M. Naquet for cells producing the 1610A1 and H155 antibodies, respectively; G. Freeman for the mCD80 cDNA;A. Holdorf for Jurkat cells expressing truncation mutants of murine CD28; R. Burack for sharing his unpublished results on cooperation of CD2 and CD28; R. Houdei for cell and antibody production; and R. Barrett for preparation of the manuscript. Supported by funds from the NIH, HHMI, the Whitaker Foundation and Irene Diamond.

PY - 2001

Y1 - 2001

N2 - According to the two-signal model of T cell activation, costimulatory molecules augment T cell receptor (TCR) signaling, whereas adhesion molecules enhance TCR-MHC-peptide recognition. The structure and binding properties of CD28 imply that it may perform both functions, blurring the distinction between adhesion and costimulatory molecules. Our results show that CD28 on naïve T cells does not support adhesion and has little or no capacity for directly enhancing TCR-MHC-peptide interactions. Instead of being dependent on costimulatory signaling, we propose that a key function of the immunological synapse is to generate a cellular microenvironment that favors the interactions of potent secondary signaling molecules, such as CD28.

AB - According to the two-signal model of T cell activation, costimulatory molecules augment T cell receptor (TCR) signaling, whereas adhesion molecules enhance TCR-MHC-peptide recognition. The structure and binding properties of CD28 imply that it may perform both functions, blurring the distinction between adhesion and costimulatory molecules. Our results show that CD28 on naïve T cells does not support adhesion and has little or no capacity for directly enhancing TCR-MHC-peptide interactions. Instead of being dependent on costimulatory signaling, we propose that a key function of the immunological synapse is to generate a cellular microenvironment that favors the interactions of potent secondary signaling molecules, such as CD28.

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DO - 10.1038/ni737

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EP - 1166

JO - Nature immunology

JF - Nature immunology

IS - 12

ER -

The immunological synapse and CD28-CD80 interactions

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