Prof. Dr. Jim Kaufman

University of Cambridge

Comparative Immunogenetics

In contrast to well-studied mammals, there are many reports of strong associations between the chicken major histocompatibility complex (MHC) and resistance to infectious disease. After some decades of work, it is clear that chickens (and apparently many if not most vertebrates outside of placental mammals) express only a single MHC class I molecule at a high level, despite having several classical class I genes, and the properties of this “dominantlyexpressed” class I molecule determine the immune response. In contrast, each human MHC haplotype expresses a multigene family of class I molecules, all of which together provide more-or-less protection to most pathogens. More recently, it has become clear that there is a hierarchy of MHC class I molecules in both chickens and humans that differ in a suite of properties. At one end of this spectrum are the “promiscuous” class I molecules that bind an astonishing variety of peptides and are associated with resistance to a range of infectious pathogens in chickens, acting as “generalists” in disease resistance. On the other end of the spectrum are the “fastidious” class I molecules that bind a very restricted range of peptides, with some of these molecules controlling progression from HIV infection to AIDs in humans, which therefore may be acting as “specialists”. This concept of generalists and specialists gives us a new way to consider the contribution of MHC molecules to immunological responses, and may have interesting consequences for medicine, evolution and conservation.”

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