Molecular basis of T cell inactivation by CTLA-4

Kyung Mi Lee; Ellen Chuang; Matthew Griffin; Roli Khattri; David K. Hong; Weiguo Zhang; David Straus; Lawrence E. Samelson; Craig B. Thompson; Jeffrey A. Bluestone

doi:10.1126/science.282.5397.2263

Molecular basis of T cell inactivation by CTLA-4

Kyung Mi Lee, Ellen Chuang, Matthew Griffin, Roli Khattri, David K. Hong, Weiguo Zhang, David Straus, Lawrence E. Samelson, Craig B. Thompson, Jeffrey A. Bluestone

Melanoma Medical Oncology

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

567 Scopus citations

Abstract

CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex ζ chain in primary T cells. The association of TCRζ with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)-induced tyrosine phosphorylation. Coexpression of the CTLA-4-associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCRζ bound to CTLA-4 and abolished the p56(lck)-inducible TCRζ-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRζ and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.

Original language	English (US)
Pages (from-to)	2263-2266
Number of pages	4
Journal	Science
Volume	282
Issue number	5397
DOIs	https://doi.org/10.1126/science.282.5397.2263
State	Published - Dec 18 1998

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title = "Molecular basis of T cell inactivation by CTLA-4",

abstract = "CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex ζ chain in primary T cells. The association of TCRζ with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)-induced tyrosine phosphorylation. Coexpression of the CTLA-4-associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCRζ bound to CTLA-4 and abolished the p56(lck)-inducible TCRζ-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRζ and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.",

author = "Lee, {Kyung Mi} and Ellen Chuang and Matthew Griffin and Roli Khattri and Hong, {David K.} and Weiguo Zhang and David Straus and Samelson, {Lawrence E.} and Thompson, {Craig B.} and Bluestone, {Jeffrey A.}",

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doi = "10.1126/science.282.5397.2263",

language = "English (US)",

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T1 - Molecular basis of T cell inactivation by CTLA-4

AU - Lee, Kyung Mi

AU - Chuang, Ellen

AU - Griffin, Matthew

AU - Khattri, Roli

AU - Hong, David K.

AU - Zhang, Weiguo

AU - Straus, David

AU - Samelson, Lawrence E.

AU - Thompson, Craig B.

AU - Bluestone, Jeffrey A.

PY - 1998/12/18

Y1 - 1998/12/18

N2 - CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex ζ chain in primary T cells. The association of TCRζ with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)-induced tyrosine phosphorylation. Coexpression of the CTLA-4-associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCRζ bound to CTLA-4 and abolished the p56(lck)-inducible TCRζ-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRζ and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.

AB - CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex ζ chain in primary T cells. The association of TCRζ with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)-induced tyrosine phosphorylation. Coexpression of the CTLA-4-associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCRζ bound to CTLA-4 and abolished the p56(lck)-inducible TCRζ-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRζ and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.

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JO - Science

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Molecular basis of T cell inactivation by CTLA-4

Abstract

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