The Major Histocompatibility Complex and its impact on human and animal health

The Major Histocompatibility Complex (MHC) is a region of the vertebrate genome encoding vital components of the immune system. One of the most diverse gene families within the complex encodes MHC molecules themselves. MHC molecules display fragments of peptides for recognition by T cells, and are thus a cornerstone of adaptive immunity. Understanding the evolution of the MHC will give us a deeper understanding of its biology, with implications for human and animal health.

Connor White is working on two MHC-related questions for his PhD:

1) In humans, MHC molecules are known as Human Leukocyte Antigens (HLAs). Connor is simulating case control studies of HLA protectiveness in the context of multi strain pathogens. This work will help us understand how best to detect whether HLA genotypes are protective against or risk factors for multi-strain diseases.

2) Humans possess just one copy of each of three class I MHC loci, but other species possess variable numbers of copies of class I MHC loci. Connor is investigating the evolutionary processes underlying this phenomenon, and their implications for animal health.

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The evolutionary dynamics of human disease resistance

When a mutation that protects against the costs of infectious disease arises in a human population, what factors promote or supress its spread?

Susie Cant’s PhD project addresses this question, taking as case studies:

1) Competition amongst mutations which confer haemoglobin-based resistance to malaria.

2) The possible impact of genetic susceptibility/resistance factors on the mass mortality events which occurred when European invaders made contact with previously isolated populations such as those of the Pacific Islands, bringing with them previously-unknown pathogens. This part of Susie's project is in collaboration with Prof Dennis Shanks.

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