TY - JOUR
T1 - Molecular basis of T cell inactivation by CTLA-4
AU - Lee, Kyung Mi
AU - Chuang, Ellen
AU - Griffin, Matthew
AU - Khattri, Roli
AU - Hong, David K.
AU - Zhang, Weiguo
AU - Straus, David
AU - Samelson, Lawrence E.
AU - Thompson, Craig B.
AU - Bluestone, Jeffrey A.
PY - 1998/12/18
Y1 - 1998/12/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032545452&partnerID=8YFLogxK
U2 - 10.1126/science.282.5397.2263
DO - 10.1126/science.282.5397.2263
M3 - Article
C2 - 9856951
AN - SCOPUS:0032545452
SN - 0036-8075
VL - 282
SP - 2263
EP - 2266
JO - Science
JF - Science
IS - 5397
ER -