The evolution of Natural Killer cell receptors: alternative strategies to recognise self and create immune variation

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• Dr John Hammond, IAH, Compton
• Wednesday 06 February 2013, 12:30-13:30
• Lecture Theatre, Department of Pathology, Tennis Court Road.

If you have a question about this talk, please contact Sue Griffin.

Host: Hannah Siddle (hvs26@cam.ac.uk)

A comparison of mammalian genomes reveals that the biggest differences are between the genes involved in the immune response and reproduction. Natural killer (NK) cells have fundamental roles in both these biological processes and are functionally controlled by variable receptors that recognise MHC class I molecules. This diverse NK cell receptor and MHC class I ligand system is therefore subject to multiple and strong selection pressures. As a consequence these gene families evolve rapidly and orthologous genes are often impossible to identify even in closely related species.

During mammalian radiation, different groups have diversified alternative NK cell receptor gene families that recognise MHC class I. This is a remarkable example of convergent evolution that includes three gene families from two structurally unrelated superfamilies (KIR, NKG2 and Ly49). Higher primates have expanded their KIR genes; some lower primates have expanded NKG2 , whereas rodents and equids have expanded Ly49. Pinnipeds (seals) are unusual, compared to other mammals and their terrestrial relatives, in retaining multiple functional NK cell receptors as single copy genes despite possessing a diverse MHC class I repertoire. In contrast, cattle have created this variation by expanding all three gene families; the only species known to have significantly expanded more than one. These alternative genetic strategies illustrate the evolutionary complexity of these systems, and present a natural reservoir of immunogenetic diversity to improve disease resistance in livestock species.

This talk is part of the Immunology in Pathology series.

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