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Title: A modern approach for epitope prediction: identification of foot-and-mouth disease virus peptides binding bovine leukocyte antigen (BoLA) class I molecules

Author
item PANDYA, MITAL - University Of Vermont
item RASMUSEN, MICHAEL - University Of Copenhagen
item HANSEN, ANDREAS - University Of Copenhagen
item NIELSEN, MORTEN - Technical University Of Denmark
item BUUS, SOREN - University Of Copenhagen
item Golde, William
item BARLOW, JOHN - University Of Vermont

Submitted to: Immunogenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/7/2015
Publication Date: 10/24/2015
Citation: Pandya, M., Rasmusen, M., Hansen, A., Nielsen, M., Buus, S., Golde, W.T., Barlow, J. 2015. A modern approach for epitope prediction: identification of foot-and-mouth disease virus peptides binding bovine leukocyte antigen (BoLA) class I molecules. Immunogenetics. 67:691-703. doi: 10.1007/s00251-015-0877-7.

Interpretive Summary: Foot and mouth disease (FMD) is a devastating viral disease of livestock. Eradicated in the United States since 1929, the FMD virus (FMDV) infects cloven hoof livestock (cattle, pigs, sheep). In an effort to understand the immunity against this virus in cattle a study was undertaken of the basic mechanisms controlling the immune response. The proteins controlling the immune response to pathogens in cattle are known as bovine leukocyte antigens, or BoLA. These proteins scan the environment in the body for invasion of pathogens. In these studies, we describe how the class I BoLA proteins bind peptides of the FMDV structural proteins. We also report FMDV peptide/BoLA class I stability, where more stable binding correlates to a stronger stimulation of the immune response. The goal is to indentify common patterns among diverse strains of FMDV that cattle (expressing different BoLA proteins) can respond to in order to design more effective vaccines.

Technical Abstract: Major histocompatibility complex (MHC) class I molecules regulate adaptive immune responses through the presentation of antigenic peptides to CD8positive T-cells. Polymorphisms in the peptide binding region of class I molecules determine peptide binding affinity and stability during antigen presentation, and different antigen peptide motifs are associated with specific genetic sequences of class I molecules. Understanding bovine leukocyte antigen (BoLA), peptide-MHC class I binding specificities may facilitate development of vaccines or reagents for quantifying the adaptive immune response to intracellular pathogens, such as foot and mouth disease virus (FMDV). Six synthetic BoLA class I (BoLA-I) molecules were produced and the peptide-binding motif was generated for five of the six molecules using a combined approach of positional scanning combinatorial peptide libraries (PSCPL) and neural network based predictions (NetMHCpan). The updated NetMHCpan server was used to predict BoLA-I binding peptides within the P1 structural polyprotein sequence of FMDV (strain A24 Cruzeiro) for BoLA-1*01901, -2*00801, -2*01201 and -4*02401. Peptide binding affinity and stability was determined for these BoLA-I molecules using the luminescent oxygen channeling immunoassay (LOCI) and scintillation proximity assay (SPA). The functional diversity of known BoLA alleles was predicted using the MHCcluster tool and functional predictions for peptide motifs were compared to observed data from this and prior studies. Results of these analyses showed that BoLA alleles cluster into three distinct groups with the potential to define ‘BoLA supertypes’. This streamlined approach identifies potential T-cell epitopes from pathogens, such as FMDV and provides insight into T-cell immunity following infection or vaccination.