Location: Foreign Animal Disease ResearchTitle: Identification of peptides fromm foot-and-mouth disease virus structural proteins bound by class I swine leucocyte antigen (SLA) alleles, SLA-1*0401 and SLA-2*0401 Author
Submitted to: Animal Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/19/2012
Publication Date: 9/18/2012
Publication URL: http://handle.nal.usda.gov/10113/57168
Citation: Pedersen, L.E., Harndahl, M., Nielsen, M., Patch, J.R., Jungersen, G., Buus, S., Golde, W.T. 2012. Identification of peptides fromm foot-and-mouth disease virus structural proteins bound by class I swine leucocyte antigen (SLA) alleles, SLA-1*0401 and SLA-2*0401. Animal Genetics. 44(3):251-258. DOI: 10.1111/j.1365-2052.2012.02400.x Interpretive Summary: The adaptive immune response of mammals is mediated by lymphocytes that can bind foreign antigens. Both the B lymphocytes, that have antibodies as receptors and T lymphocytes expressing a T cell receptor, exquisitely differentiate a normal cell from a cell infected with virus. Where antibodies on B cells can directly bind foreign antigens, T cells see small peptides bound by major histocompatibility complex (MHC) proteins. These highly polymorphic, cell surface proteins are the “transplantation” antigens that have to be matched between donors and recipients to ensure successful organ transplants. Class I MHC proteins scan the intracellular environment and class II MHC proteins scan the extracellular space for antigenic peptides. When a peptide is derived from normal proteins of the cell and bound by a MHC protein, the cell looks like self to the immune system. However, when the protein is derived from a virus or other foreign entity, the cell looks foreign and triggers a cellular immune response. The responding, antigen specific T cell activates adaptive immune responses by proliferating and signaling B lymphocytes to make antibody and cytotoxic T lymphocytes to kill virus infected cells. Previously, we described the first analysis of a swine MHC protein (SLA-1) for binding of peptide antigens, thus defining what peptides are capable of stimulating T cells. Here we now analyze a second swine MHC protein, SLA-2, and apply the peptide antigen binding data to an analysis of the structural proteins of foot-and-mouth disease virus (FMDV). These data provide the first biochemical evidence of what T cell antigens of FMDV look like in the context of a genetically defined swine population.
Technical Abstract: The analysis of peptide binding to porcine major histocompatibility complex (MHC) class I molecules has not been extensively performed. Critical to understanding the adaptive immune response of swine to infection is characterization of Swine Leucocyte Antigens (SLA) class I and class II peptide binding capacity, which determines immunogenic epitopes of any given pathogen proteome. Here, we describe the complete binding motif for the SLA-2*0401 molecule based on a peptide library approach. By combining such determined binding motifs with data achieved by applying the NetMHCpan peptide prediction algorithm to both SLA-1*0401 and SLA-2*0401, we identify peptides with high binding affinity. Using these approaches, we identified 9 and 10 amino acid peptides as candidate T cell epitopes from a total of 727 different 9mer and 726 different 10mer peptides within the structural proteins of FMDV, strain A24. These peptides were tested in ELISA for binding by the SLA-1*0401 and SLA-2*0401 MHC class I proteins. Four of the ten predicted FMDV peptides were bound by SLA-2*0401 whereas five out of the nine predicted FMDV peptides were bound by SLA-1*0401. In addition, two peptides from both Ebola virus and Vibrio cholera proteins, were bound by both alleles, as predicted by the algorithm. These methods will allow the characterization of T cell responses to pathogens in more detail. The development of such approaches to analysis of vaccine performance will contribute to a more accelerated improvement of livestock vaccines by virtue of identifying and focusing analysis on bona fide T cell epitopes.