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

Research output: Contribution to journalArticle

464 Citations (Scopus)

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 languageEnglish
Pages (from-to)2263-2266
Number of pages4
JournalScience
Volume282
Issue number5397
DOIs
Publication statusPublished - 1998 Dec 18
Externally publishedYes

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T-Cell Antigen Receptor
T-Lymphocytes
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Tyrosine
Phosphorylation
Phosphoric Monoester Hydrolases
Signal Transduction

ASJC Scopus subject areas

  • General

Cite this

Lee, K-M., Chuang, E., Griffin, M., Khattri, R., Hong, D. K., Zhang, W., ... Bluestone, J. A. (1998). Molecular basis of T cell inactivation by CTLA-4. Science, 282(5397), 2263-2266. https://doi.org/10.1126/science.282.5397.2263

Molecular basis of T cell inactivation by CTLA-4. / Lee, Kyung-Mi; Chuang, Ellen; Griffin, Matthew; Khattri, Roli; Hong, David K.; Zhang, Weiguo; Straus, David; Samelson, Lawrence E.; Thompson, Craig B.; Bluestone, Jeffrey A.

In: Science, Vol. 282, No. 5397, 18.12.1998, p. 2263-2266.

Research output: Contribution to journalArticle

Lee, K-M, Chuang, E, Griffin, M, Khattri, R, Hong, DK, Zhang, W, Straus, D, Samelson, LE, Thompson, CB & Bluestone, JA 1998, 'Molecular basis of T cell inactivation by CTLA-4', Science, vol. 282, no. 5397, pp. 2263-2266. https://doi.org/10.1126/science.282.5397.2263
Lee K-M, Chuang E, Griffin M, Khattri R, Hong DK, Zhang W et al. Molecular basis of T cell inactivation by CTLA-4. Science. 1998 Dec 18;282(5397):2263-2266. https://doi.org/10.1126/science.282.5397.2263
Lee, Kyung-Mi ; Chuang, Ellen ; Griffin, Matthew ; Khattri, Roli ; Hong, David K. ; Zhang, Weiguo ; Straus, David ; Samelson, Lawrence E. ; Thompson, Craig B. ; Bluestone, Jeffrey A. / Molecular basis of T cell inactivation by CTLA-4. In: Science. 1998 ; Vol. 282, No. 5397. pp. 2263-2266.
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