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Regulation through inhibitory receptors: Lessons from natural killer cells

D N Burshtyn, E O Long

    Trends in Cell Biology
    |August 22, 2007
    PubMed

    Insights

    Natural killer (NK) cells kill targets lacking inhibitory ligands. This cytotoxicity is regulated by inhibitory receptors activating the SHP-1 phosphatase via an immunoreceptor tyrosine-based inhibitory motif (ITIM).

    Area of Science:

    • Immunology
    • Cell Biology

    Background:

    • Natural killer (NK) cells possess unique recognition capabilities, eliminating target cells deficient in ligands for inhibitory NK cell receptors.
    • NK cell cytotoxicity is precisely regulated by inhibitory receptors that recruit and activate the tyrosine phosphatase SHP-1.

    Purpose of the Study:

    • To investigate the mechanism of NK cell cytotoxicity regulation.
    • To identify the key molecular components involved in inhibitory signaling.

    Main Methods:

    • Analysis of the cytoplasmic tail of inhibitory NK cell receptors.
    • Identification of conserved amino acid sequence motifs.

    Main Results:

    • The tyrosine-phosphorylated [I/V]xYxxL amino acid sequence, known as an immunoreceptor tyrosine-based inhibitory motif (ITIM), is crucial for SHP-1 recruitment and activation.
    • This ITIM motif is present in the cytoplasmic tail of inhibitory NK cell receptors.

    Conclusions:

    • The ITIM motif mediates inhibitory signals by recruiting and activating SHP-1, thereby controlling NK cell cytotoxicity.
    • This inhibitory mechanism involving ITIMs is likely a widespread regulatory strategy across various cell types and cellular responses.

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