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

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• 作者：Mital Pandya ; Michael Rasmussen ; Andreas Hansen ; Morten Nielsen…
• 关键词：MHC class I ; Motif ; Peptide ; FMDV ; Epitope ; Immunoinformatics
• 刊名：Immunogenetics
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：67
• 期：11-12
• 页码：691-703
• 全文大小：1,250 KB
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• 作者单位：Mital Pandya (1)
  Michael Rasmussen (2)
  Andreas Hansen (2)
  Morten Nielsen (3) (4)
  Soren Buus (2)
  William Golde (5)
  John Barlow (1)
  
  1. Department of Animal Science, University of Vermont, 570 Main Street, 221 Terrill Building, Burlington, VT, 05405, USA
  2. Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, DK-2200, Denmark
  3. Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark
  4. Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Buenos Aires, Argentina
  5. Plum Island Animal Disease Center, Agricultural Research Service, USDA, Greenport, NY, 11944, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Immunology
  Allergology
  Cell Biology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1211

文摘

Major histocompatibility complex (MHC) class I molecules regulate adaptive immune responses through the presentation of antigenic peptides to CD8+ 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 (PSCPLs) 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, BoLA-2*00801, BoLA-2*01201, and BoLA-4*02401. Peptide binding affinity and stability were 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. The 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. Keywords MHC class I Motif Peptide FMDV Epitope Immunoinformatics