Molecular Basis of T Cell Inactivation by CTLA-4
- 18 December 1998
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 282 (5397) , 2263-2266
- https://doi.org/10.1126/science.282.5397.2263
Abstract
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.Keywords
This publication has 26 references indexed in Scilit:
- Fidelity of T Cell Activation Through Multistep T Cell Receptor ζ PhosphorylationScience, 1998
- The Emerging Role of CTLA-4 as an Immune AttenuatorImmunity, 1997
- Human Influence on the Atmospheric Vertical Temperature Structure: Detection and ObservationsScience, 1996
- The Complexities of T‐Cell Co‐stimulation: CD28 and BeyondImmunological Reviews, 1996
- Intracellular Trafficking of CTLA-4 and Focal Localization Towards Sites of TCR EngagementPublished by Elsevier ,1996
- Regulation of T Cell Receptor Signaling by Tyrosine Phosphatase SYP Association with CTLA-4Science, 1996
- Abdominal Reservoirs for Continent Urinary DiversionJournal of Urology, 1995
- CTLA-4 can function as a negative regulator of T cell activationImmunity, 1994
- SH2-Containing Phosphotyrosine Phosphatase as a Target of Protein-Tyrosine KinasesScience, 1993
- A new subunit of the human T-cell antigen receptor complexNature, 1986