BBSRC studentship: Phenotypic and functional characterisation of cattle natural killer (NK) cell clones

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Studentship, Natural killer (NK) cells play an important role in innate resistance to many cattle pathogens, including Mycobacterium bovis, the causative agent of tuberculosis. They express an array of membrane-bound receptors that largely control the NK response to infection. Many recognise subsets of ubiquitously expressed MHC class I genes, and NK cell function is to a large extent controlled by the balance of expressed inhibitory and activating receptors with shared ligands. MHC class I genetics and expression are complex in cattle, and we have recently demonstrated equivalent complexity in some NK receptor (NKr) gene families. Different clones of NK cells within an individual may each express a distinct complement of receptors. Coupled with extensive haplotype variation in both MHC class I and NKr genes, this suggests a complex interplay in cattle involving NK cells, receptors, their ligands and potentially also pathogens that may subvert MHC expression. The aim of this project is to gain insight into this interplay, leading to strategies (selective breeding / improved vaccine design) to increase disease resistance in commercial cattle herds. Data generated will also shed light on evolution of the mammalian immune system. The project will involve generation and maintenance of phenotypically distinct sets of NK clones from animals expressing characterised MHC class I haplotypes. NK clones will be characterised using flow cytometry with mAbs recognising NKr, and RT-PCR from cDNA using gene-specific primers. Functional differences between clones will be established by measuring cytotoxicity and cytokine production. The response of NK clones to cells expressing different MHC class I genes will be measured. Changes in expression of NKr genes will be assessed in a small number of MHC-defined animals in response to infection or vaccination. Reagents and data for the work are being generated during the course of on-going projects within the PI's group.

unavailable