Molecular Basis of T Cell Inactivation by CTLA-4

• DOI: 10.1126/science.282.5397.2263
• Publication Date: 2002-07-27T09:37:56Z
• Authors: 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
• Keywords: Dephosphorylation; Negative regulator; CTLA-4; Jurkat cells

CTLA-4, a negative regulator of T cell function, was found to associate with the receptor (TCR) complex ζ chain in primary cells. The association TCRζ reconstituted 293 transfectants, enhanced by p56 lck -induced tyrosine phosphorylation. Coexpression CTLA-4–associated phosphatase, SHP-2, resulted dephosphorylation bound CTLA-4 and abolished -inducible TCRζ–CTLA-4 interaction. Thus, inhibits TCR signal transduction binding inhibiting phosphorylation after activation. These findings have broad implications for regulation function tolerance.