Here we report the sequence of the region that determines rapid allograft rejection in chickens, the chicken major histocompatibility complex (MHC). This 92-kilobase region of the B locus1,2,3,4 contains only 19 genes, making the chicken MHC roughly 20-fold smaller than the human MHC5. Virtually all the genes have counterparts in the human MHC, defining a minimal essential set of MHC genes conserved over 200 million years of divergence between birds and mammals. They are organized differently, with the class III region genes located outside the class II and class I region genes. The absence of proteasome genes5,6 is unexpected and might explain unusual peptide-binding specificities of chicken class I molecules. The presence of putative natural killer receptor gene(s)5,7 is unprecedented and might explain the importance of the B locus in the response to the herpes virus responsible for Marek's disease8,9,10. The small size and simplicity of the chicken MHC allows co-evolution of genes as haplotypes over considerable periods of time, and makes it possible to study the striking MHC-determined pathogen-specific disease resistance8,9,10 at the molecular level.
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We thank I. Shaw, T. Powell, S. Rogers, A. Smith, P. Kaiser and G. Griffiths for help with analysis and/or critical review of the manuscript. S.M. and S.B. are funded by the Wellcome Trust and, at the early stage of the project, by the Imperial Cancer Research Fund and a grant from the EU BioMed 1 programme. J.J. is supported by the EU FAIR program.
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