Molecular Basis of T Cell Inactivation by CTLA-4

0301 basic medicine Mice, Inbred BALB C Immunoconjugates Protein Tyrosine Phosphatase, Non-Receptor Type 6 Intracellular Signaling Peptides and Proteins Models, Immunological Membrane Proteins Protein Tyrosine Phosphatase, Non-Receptor Type 11 Lymphocyte Activation Antigens, Differentiation Cell Line Abatacept Mice 03 medical and health sciences 0302 clinical medicine Antigens, CD Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Animals Humans CTLA-4 Antigen Phosphorylation Phosphotyrosine Cells, Cultured
DOI: 10.1126/science.282.5397.2263 Publication Date: 2002-07-27T09:37:56Z
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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (35)
CITATIONS (543)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....