Quantifying the reduction in accessibility of the inhibitory NK cell receptor Ly49A caused by binding MHC class I proteins in cis

Katja E. Andersson, Geoffrey S. Williams, Daniel M. Davis, Petter Höglund

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Murine natural killer (NK) cells are inhibited by target cell MHC class I molecules via Ly49 receptors. However, Ly49 receptors can be made inaccessible to target cell MHC class I by a cis interaction with its MHC class I ligand within the NK cell membrane. It has recently been demonstrated that MHC class I proteins transfer from the target cells to the NK cell. Here, we establish that the number of transferred MHC class I proteins is proportional to the number of Ly49A receptors at the NK cell surface. Ly49A+ NK cells from mice expressing the Ly49A ligand H-2Dd d showed a 90% reduction in Ly49A+ accessibility compared to Ly49A+ NK cells from H-2Dd - negative mice. The reduction was caused both by lower expression of Ly49A and interactions in cis between Ly49A and H-2Dd at the NK cell surface. Approximately 75% of the Ly49A receptors on H-2Dd-expressing NK cells were occupied in cis with endogenous H-2Dd and only 25% were free to interact with H-2Dd molecules in trans. Thus, H-2Dd ligands control Ly49A receptor accessibility through interactions both in cis and in trans. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Original languageEnglish
    Pages (from-to)516-527
    Number of pages11
    JournalEuropean journal of immunology
    Volume37
    Issue number2
    DOIs
    Publication statusPublished - Feb 2007

    Keywords

    • Cis interaction
    • Immune synapse
    • Ly49
    • MHC class I
    • NK cell

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