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

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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 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
Issue number5397
Publication statusPublished - 1998 Dec 18

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    Lee, K. M., Chuang, E., Griffin, M., Khattri, R., Hong, D. K., Zhang, W., Straus, D., Samelson, L. E., Thompson, C. B., & Bluestone, J. A. (1998). Molecular basis of T cell inactivation by CTLA-4. Science, 282(5397), 2263-2266.