A peptide antagonist disrupts NK Cell inhibitory synapse formation

Gwenoline Borhis, Parvin S. Ahmed, Bérénice Mbiribindi, Mohammed M. Naiyer, Daniel M. Davis, Marco A. Purbhoo, Salim I. Khakoo

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Productive engagement of MHC class I by inhibitory NK cell receptors depends on the peptide bound by the MHC class I molecule. Peptide:MHC complexes that bind weakly to killer cell Ig-like receptors (KIRs) can antagonize the inhibition mediated by highaffinity peptide:MHC complexes and cause NK cell activation. We show that low-affinity peptide:MHC complexes stall inhibitory signaling at the step of Src homology protein tyrosine phosphatase 1 recruitment and do not go on to form the KIR microclusters induced by high-affinity peptide:MHC, which are associated with Vav dephosphorylation and downstream signaling. Furthermore, the low-affinity peptide:MHC complexes prevented the formation of KIR microclusters by high-affinity peptide:MHC. Thus, peptide antagonism of NK cells is an active phenomenon of inhibitory synapse disruption. © 2013 by The American Association of Immunologists, Inc.
    Original languageEnglish
    Pages (from-to)2924-2930
    Number of pages6
    JournalJournal of Immunology
    Volume190
    Issue number6
    DOIs
    Publication statusPublished - 15 Mar 2013

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