Typing MHC haplotypes of African village chickens for structure-function studies Jim Kaufman1,2, Rebecca Martin 1, Jacqueline Smith3, Mike McGrew3, Clive Tregaskes1, 1Department of Pathology, University of Cambridge; 2Department of Veterinary Medicine, University of Cambridge; 3Roslin Institute, University of Edinburgh
The highly polymorphic class I and class II molecules encoded by the major histocompatibility complex (MHC) present antigenic peptides to T lymphocytes as well as class I molecules being recognized by natural killer (NK) cells, and so they play central roles in adaptive and innate immune responses. Unlike in mammals, the chicken MHC can determine truly significant levels of resistance or susceptibility to particular infectious pathogens, at least in part due to the fact that only single MHC class I and class II genes are widely and strongly expressed in chickens. We have determined peptide motifs and crystallographic structures for several chicken class I and class II molecules, and found that some class I molecules (that act as generalists) confer resistance to many common pathogens. We have developed a PCR-next generation sequencing (NGS) method that types the exons encoding the peptide-binding regions of all class I and class II genes for up to 1200 chickens at a time, starting with a few blood cells. With many collaborators around the world who have contributed samples, we are using the typing system to understand the population genetics of MHC genes and haplotypes, and to underpin structural and functional studies that can be translated into breeding for disease resistance and vaccine response, among other uses.
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