Download MendeleyIllumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I).
Pan, X., Zhang, N., Wei, X., Jiang, Y., Chen, R., Li, Q., Liang, R., Zhang, L., Ma, L., Xia, C.(2019) Front Immunol 10: 2995-2995
- PubMed: 31969884
- DOI: https://doi.org/10.3389/fimmu.2019.02995
- Primary Citation of Related Structures:
5YLX - PubMed Abstract:
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-γ 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.
Organizational Affiliation:
Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
