Molecular basis of T cell inactivation by CTLA-4.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Lee, KM; Chuang, E; Griffin, M; Khattri, R; Hong, DK; Zhang, W; Straus, D; Samelson, LE; Thompson, CB; Bluestone, JA

Published Date

  • December 18, 1998

Published In

Volume / Issue

  • 282 / 5397

Start / End Page

  • 2263 - 2266

PubMed ID

  • 9856951

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.282.5397.2263


  • eng

Conference Location

  • United States