Completed Genetics & Molecular Biology Infection & Immunity

Understanding the basis and impact of gene co-evolution within the chicken MHC.

In plain English

AI plain-English summary

Chickens carry a genetic region called the MHC that dictates how their immune system recognises viruses and other threats, and this project will map how its genes evolve together as a single, co-dependent unit. Most research on the chicken MHC has focused on a few laboratory lines, leaving the full genetic diversity of commercial and village chickens unexplored. This matters because the MHC controls whether a bird mounts a strong immune response to a vaccine or succumbs to a disease like Marek’s virus or avian influenza. Without knowing how MHC genes co-evolve in real-world populations, breeders and vets cannot predict which birds will resist infection or respond poorly to vaccination. The team will sequence MHC genes from a wide range of chickens, determine which short protein fragments each MHC variant presents to immune cells, and analyse the molecular interactions between antigen-processing proteins (TAP1, TAP2, tapasin) and the receptors on killer T cells and natural killer cells. If successful, this fundamental science will reveal the rules governing MHC co-evolution in birds. That knowledge could eventually help poultry breeders select for disease-resistant flocks and improve vaccine design, but the immediate payoff is a deeper understanding of how immune genes shape each other’s evolution—a question that applies to all vertebrates, including humans.

View original technical description
Our overall goal is to understand the basis for and the impact of gene co-evolution within the chicken MHC, focusing on those genes involved in class I antigen presentation. Aim 1. Develop and use methods to type, sequence, and determine the peptide motifs for chicken class I (and other) genes, extending the analysis of co-evolution of MHC genes from a few experimental lines to a full range of chickens in order to understand the genetic basis of the co-evolution of chicken MHC genes, to lay the basis for structure/function studies and to lay the basis for an analysis of disease resistance and vaccine response in the field. Aim 2. Analyse the chicken molecules involved in antigen processing, particularly TAP1, TAP2 and tapasin which are highly polymorphic, in order to understand the basis of the molecular interactions resulting from the co-evolution of chicken MHC genes. Aim 3. Analyse the effector cells and molecules involved in recognition of chicken class I molecules, parti cularly cytotoxic T lymphocytes (CTLs) and T cell receptors (TcR) as well as natural killer (NK) cells and NK cell receptors (NKr), in order to understand the impact of the co-evolution of chicken MHC genes on the immune response.

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Researchers

James Kaufman (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Comparative studies to understand the role of class II molecules expressed in epithelial cells.
Understanding the contribution of immune genes to disease resistance in an economically important farm animal, the chicken
ANIHWA call2: Understanding mucosal immunology and co-infections in the chicken to drive vaccine strategies
Identification of genetic variation in innate immune response genes associated with resistance to chicken viral infections
A multi-level study of peptide editing in the MHC class I antigen processing pathway and its immunological consequences

Original classification

Programme Grant

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