Cutting edge: tyrosine-independent transmission of inhibitory signals by CTLA-4
T Cinek, A Sadra, JB Imboden - The Journal of Immunology, 2000 - journals.aai.org
T Cinek, A Sadra, JB Imboden
The Journal of Immunology, 2000•journals.aai.orgCTLA-4 is an important inhibitor of T cell activation. We used Jurkat cells expressing mutants
of murine CTLA-4 to study the structural requirements for inhibitory signaling. We find that
signals for the inhibition of IL-2 secretion are delivered efficiently by a CTLA-4 mutant in
which both cytoplasmic tyrosines have been replaced by phenylalanines. A CTLA-4 mutant
that lacks the carboxyl-terminal half of the intracellular domain also retains the ability to
inhibit, but deletion of an additional 11 aa completely abrogates that capability. We conclude …
of murine CTLA-4 to study the structural requirements for inhibitory signaling. We find that
signals for the inhibition of IL-2 secretion are delivered efficiently by a CTLA-4 mutant in
which both cytoplasmic tyrosines have been replaced by phenylalanines. A CTLA-4 mutant
that lacks the carboxyl-terminal half of the intracellular domain also retains the ability to
inhibit, but deletion of an additional 11 aa completely abrogates that capability. We conclude …
Abstract
CTLA-4 is an important inhibitor of T cell activation. We used Jurkat cells expressing mutants of murine CTLA-4 to study the structural requirements for inhibitory signaling. We find that signals for the inhibition of IL-2 secretion are delivered efficiently by a CTLA-4 mutant in which both cytoplasmic tyrosines have been replaced by phenylalanines. A CTLA-4 mutant that lacks the carboxyl-terminal half of the intracellular domain also retains the ability to inhibit, but deletion of an additional 11 aa completely abrogates that capability. We conclude that delivery of an inhibitory signal requires the membrane-proximal region of the CTLA-4 cytoplasmic domain and does not depend upon the tyrosine phosphorylation of CTLA-4.
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