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Human NK Cell Receptor Diversity Shaped by Natural Selection

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If you have a question about this talk, please contact Prof. Jim Kaufman.

Host: John Trowsdale (jt233@cam.ac.uk)

The interaction of natural killer (NK) cell receptors with MHC Class I ligands modulates NK cell development and activity, to aid combating disease or during pregnancy. We have been investigating the genetic diversity of human NK receptors, and how they have evolved to interact with the highly polymorphic HLA system. We have been performing large-scale genetic studies of killer cell immunoglobulin-like receptors (KIR), and the population genetics shows that strong balancing selection is acting on the KIR molecules. We also demonstrate co-evolution of HLA and KIR that has been targeted specifically to the amino acids that influence their interaction. The hypotheses that we derive from population genetic and sequence-based analysis are tested in the laboratory, and this is showing that the naturally-selected variation directly affects NK cell function. Taken together we are uncovering enormous potential for genetically-defined variety in human immune function.

This talk is part of the Immunology in Pathology series.

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