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Molecular basis of T cell inactivation by CTLA-4.

Publication ,  Journal Article
Lee, KM; Chuang, E; Griffin, M; Khattri, R; Hong, DK; Zhang, W; Straus, D; Samelson, LE; Thompson, CB; Bluestone, JA
Published in: Science
December 18, 1998

CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex zeta chain in primary T cells. The association of TCRzeta 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 TCRzeta bound to CTLA-4 and abolished the p56(lck)-inducible TCRzeta-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRzeta 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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Published In

Science

DOI

ISSN

0036-8075

Publication Date

December 18, 1998

Volume

282

Issue

5397

Start / End Page

2263 / 2266

Location

United States

Related Subject Headings

  • src Homology Domains
  • Transfection
  • T-Lymphocytes
  • Signal Transduction
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • Recombinant Fusion Proteins
  • Receptors, Antigen, T-Cell
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
 

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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
Lee, K. M., E. Chuang, M. Griffin, R. Khattri, D. K. Hong, W. Zhang, D. Straus, L. E. Samelson, C. B. Thompson, and J. A. Bluestone. “Molecular basis of T cell inactivation by CTLA-4.Science 282, no. 5397 (December 18, 1998): 2263–66. https://doi.org/10.1126/science.282.5397.2263.
Lee KM, 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):2263–6.
Lee, K. M., et al. “Molecular basis of T cell inactivation by CTLA-4.Science, vol. 282, no. 5397, Dec. 1998, pp. 2263–66. Pubmed, doi:10.1126/science.282.5397.2263.
Lee KM, Chuang E, Griffin M, Khattri R, Hong DK, Zhang W, Straus D, Samelson LE, Thompson CB, Bluestone JA. Molecular basis of T cell inactivation by CTLA-4. Science. 1998 Dec 18;282(5397):2263–2266.
Journal cover image

Published In

Science

DOI

ISSN

0036-8075

Publication Date

December 18, 1998

Volume

282

Issue

5397

Start / End Page

2263 / 2266

Location

United States

Related Subject Headings

  • src Homology Domains
  • Transfection
  • T-Lymphocytes
  • Signal Transduction
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • Recombinant Fusion Proteins
  • Receptors, Antigen, T-Cell
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11