T-cell responses to influenza virus in pigs

The tools and techniques for the study of porcine T-cells lag behind what is currently attainable in human T-cells, so this thesis was initially focused on improvements in this field. This study established long-term culture of porcine T-cells, T-cell clone procurement and relevant T-cell assays. These techniques were then used to investigate cytotoxic T-cell responses to Influenza A virus (IAV) in pigs. IAV is highly mutative and novel strains can be generated following reassortment between different viral strains. IAV is endemic in the global pig population and in some circumstances the virus can pass between humans and pigs and other animals. Pigs can therefore, potentially be a source for the generation of new and possibly pandemic influenza strains. The risk this poses to global human health, together with the negative effects of IAV infection within pig herds, highlights the need to improve our knowledge of IAV in pigs. This study identified four new MHC class I restricted IAV epitopes, derived from the viral nucleoprotein. Cytotoxic T-cells recognising these IAV epitopes were detected at high numbers ex vivo in samples from vaccinated pigs. The structures of these IAV epitopes in complex with their respective MHC class I molecules were resolved and revealed the primary anchor positions within the peptides. This enabled peptide binding motifs to be defined for two porcine MHC-I alleles. These peptide binding motifs can be utilised for efficient epitope prediction. This study also identified super-agonist ligands for two of the MHC-I restricted IAV epitopes. Overall, this work has opened up the study of porcine T-cells to a level previously unattainable and has contributed to our knowledge of IAV in pigs. It has paved the way for further experiments investigating IAV in pigs, other porcine diseases and for using pigs as an animal model for human disease.