BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:Just how do the poor chickens survive all those pathogens? - Profe ssor Jim Kaufman DTSTART:20140312T161500Z DTEND:20140312T171500Z UID:TALK49380@talks.cam.ac.uk CONTACT:Fiona Roby DESCRIPTION:At least 50 billion (that is\, thousand million) chickens prov ide eggs and meat each year\, the vast majority being commercial meat chic kens originating from two global poultry breeding companies. Most chickens are densely-stocked under conditions which favour transmission of a huge range of pathogens. Vaccination is a major method for controlling disease but usually not transmission\, leading to evolution of pathogens with chan ges in antigenicity\, virulence and/or tropism. Another mode of protection is genetic resistance\, for which there is much evidence in chickens\, pa rticularly for the major histocompatibility complex (MHC). \nMHC class I a nd class II molecules bind pieces of antigen (usually peptides derived fro m proteins\, both self and non-self) and bring them to the surface of the cell where they can be recognised by T lymphocytes\, a process termed “a ntigen presentation”. MHC molecules are generally highly polymorphic\, w ith many alleles and much variation in sequence\, mainly clustered around the peptide-binding groove. This variation (or “polymorphism”) is thou ght to be mainly driven by a molecular arms race with pathogens\, which pr edicts that the MHC should strongly determine resistance and susceptibilit y to pathogens. There are many strong associations of the chicken MHC with infectious diseases\, but the strong associations for the human MHC are w ith autoimmune diseases. \nOver the last 20 years\, we have provided a mol ecular explanation for this functional difference\, which is rooted in the evolutionary history of the MHC\, particularly changes in genomic organis ation that affect the interaction between proteins of the antigen presenta tion pathway. The result is that humans and most placental mammals express a multi-gene family of MHC molecules at high levels\, so that each MHC ha plotype confers more-or-less resistance to most pathogens\, leading to wea k genetic associations. In contrast\, each chicken MHC haplotype expresses only one class I molecule (and one class II molecule) at a high level\, a nd the properties of this “dominantly-expressed” MHC molecule in large part determines the immune response\, leading to strong genetic associati ons. For a couple of viral infections and vaccinations\, we have shown tha t the peptide-binding specificity of the particular MHC class I molecule c an explain life or death of particular chickens. \nSo\, how do chickens su rvive all those pathogens\, given that they have only a single dominantly- expressed MHC class I molecule? We have found that some haplotypes have cl ass I molecules with peptide-binding specificities that are really “fast idious”\, requiring particular amino acids as “anchor residues” in a t least three places within an eight amino acid peptide. However\, other h aplotypes have peptide-binding specificities that are really “promiscuou s”\, binding an astonishing variety of peptides. These two kinds of hapl otypes differ in a suite of properties\, including cell surface expression level\, peptide-transporter (“TAP”) specificity and resistance to the oncogenic herpesvirus that causes Marek’s disease. Our current hypothes is is that the promiscuous MHC molecules allow recognition by a much wider variety of T cells\, resulting in a great and more effective immune respo nse. Moreover\, we find that haplotypes with promiscuous MHC molecules are extremely common among commercial meat chickens. Thus\, it may be that co mmercial chickens survive their pathogens because they have MHC class I mo lecules that are generalists\, much more like class II molecules than like human class I molecules. \n LOCATION:Lecture Theatre 2\, Department of Veterinary Medicine END:VEVENT END:VCALENDAR