Journal
FRONTIERS IN IMMUNOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.02995
Keywords
SLA; structure; CTL; epitope; PRRSV; vaccine
Categories
Funding
- 863 Project of the China Ministry of Science and Technology [2013AA102503]
- National Natural Science Foundation of China [31201887]
- 973 Project of the China Ministry of Science and Technology [2013CB835302]
- Beijing Natural Science Foundation [6182029]
- Science and Technology Program of Anhui Province [1704A07020066]
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To investigate CTL epitope applications in swine, SLA-1*1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. First, nine predicted PRRSV peptides were tested by assembly of the peptide-SLA-1*1502 (pSLA-1*1502) complexes, and the crystal structure of the SLA-1*1502 complex with one peptide (NSP9-TMP9) was determined. The NSP9-TMP9 peptide conformation presented by pSLA-1*1502 is different from that of the peptides presented by the known pSLA-1*0401 and pSLA-3*hs0202 complexes. Two consecutive Pro residues make the turn between P3 and P4 of NSP9-TMP9 much sharper. The D pocket of pSLA-1*1502 is unique and is important for peptide binding. Next, the potential SLA-1*1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1*1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide. The tetrameric complex of SLA-1*1502 and NSP9-TMP9 was constructed and examined. Finally, taking NSP9-TMP9 as an example, the CTL immunogenicity of the identified PRRSV peptide epitope was evaluated. The SPF swine expressing the SLA-1*1502 alleles were divided into three groups: modified live vaccine (MLV), MLV+NSP9-TMP9, and the blank control group. NSP9-TMP9 was determined as a PRRSV CTL epitope with strong immunogenicity by flow cytometry and IFN-gamma expression. Our study developed an integrated approach to identify SLA-I-restricted CTL epitopes from various important viruses and is helpful in designing and applying effective peptide-based vaccines for swine.
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