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Recognition of Peptide-MHC Class I Complexes by Activating Killer Immunoglobulin-Like Receptors
C. Andrew Stewart, Fanny Laugier-Anfossi, Frédéric Vély, Xavier Saulquin, Jenifer Riedmuller, Agnès Tisserant, Laurent Gauthier, François Romagné, Géraldine Ferracci, Fernando A. Arosa, Alessandro Moretta, Peter D. Sun, Sophie Ugolini, Eric Vivier and Peter Cresswell
Proceedings of the National Academy of Sciences of the United States of America
Vol. 102, No. 37 (Sep. 13, 2005), pp. 13224-13229
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3376544
Page Count: 6
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Inhibitory receptors for MHC class I molecules increase the threshold of lymphocyte activation. Natural Killer (NK) cells express a large number of such inhibitory receptors, including the human killer Ig-like receptors (KIR). However, activating members of the KIR family have poorly defined ligands and functions. Here we describe the use of activating KIR tetramer reagents as probes to detect their ligands. Infection of cells with Epstein-Barr virus leads to expression of a detectable ligand for the activating receptor KIR2DS1. In this case, KIR2DS1 interacts with up-regulated peptide-MHC class I complexes on Epstein-Barr virus-infected cells in a transporter associated with antigen processing (TAP)-dependent manner. In tetramer-based cellular assays and direct affinity measurements, this interaction with MHC class I is facilitated by a broad spectrum of peptides. KIR2DS1 and its inhibitory homologue, KIR2DL1, share sensitivity to peptide sequence alterations at positions 7 and 8. These results fit a model in which activating and inhibitory receptors recognize the same sets of self-MHC class I molecules, differing only in their binding affinities. Importantly, KIR2DS1 is not always sufficient to trigger NK effector responses when faced with cognate ligand, consistent with fine control during NK cell activation. We discuss how our results for KIR2DS1 and parallel studies on KIR2DS2 relate to the association between activating KIR genes and susceptibility to autoimmune disorders.
Proceedings of the National Academy of Sciences of the United States of America © 2005 National Academy of Sciences