Molecular Basis of T Cell Inactivation by CTLA-4

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Science  18 Dec 1998:
Vol. 282, Issue 5397, pp. 2263-2266
DOI: 10.1126/science.282.5397.2263

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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 p56lck-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 p56lck-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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: jbluest{at}

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