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Related Experiment Videos

T cell receptor tyrosine phosphorylation. Variable coupling for different activating ligands.

R D Klausner, J J O'Shea, H Luong

    The Journal of Biological Chemistry
    |September 15, 1987
    PubMed
    Summary
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    Cell-surface molecules involved in T-cell functions.

    Immunology today·2014

    T cell activation involves two kinases phosphorylating the T cell receptor (TCR). Antigen stimulation activates both pathways, while antibodies activate them differently, impacting cAMP sensitivity.

    Area of Science:

    • Immunology
    • Cellular Signaling
    • Biochemistry

    Background:

    • T cell activation involves distinct biochemical pathways.
    • T cell receptor (TCR) stimulation activates two protein kinases.
    • These kinases phosphorylate specific chains of the TCR complex.

    Purpose of the Study:

    • To investigate the dual kinase activation in T cells upon stimulation.
    • To compare the signaling pathways activated by antigen versus antibodies targeting the TCR or Thy-1.
    • To elucidate the role of cyclic AMP (cAMP) in modulating these activation pathways.

    Main Methods:

    • Stimulation of T cells using specific antigens, anti-TCR epsilon chain antibodies, and anti-Thy-1 antibodies.
    • Analysis of protein kinase activation and phosphorylation of TCR complex chains (gamma, epsilon, p21).

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  • Assessment of the sensitivity of these pathways to cAMP inhibition.

    • Main Results:

    • Antigen stimulation activates both protein kinase C (serine phosphorylation) and an unidentified tyrosine kinase (p21 tyrosine phosphorylation).
    • Antibodies targeting the TCR or Thy-1 also induce dual kinase activation.
    • Phosphatidylinositol breakdown and serine phosphorylation are cAMP-sensitive for all stimuli.
    • Tyrosine kinase activation by antigen is cAMP-sensitive, but antibody-induced tyrosine kinase activation is cAMP-insensitive.

    Conclusions:

    • T cell activation via antigen and antibodies triggers distinct signaling kinetics.
    • cAMP differentially regulates tyrosine kinase activation depending on the stimulus.
    • These findings highlight the complex regulation of T cell activation pathways.