Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I)

文献类型： 外文期刊

第一作者： Pan, Xiaocheng

作者： Pan, Xiaocheng;Zhang, Nianzhi;Wei, Xiaohui;Jiang, Yinan;Chen, Rong;Li, Qirun;Liang, Ruiying;Zhang, Lijie;Ma, Lizhen;Xia, Chun;Pan, Xiaocheng;Xia, Chun

作者机构：

关键词： SLA; structure; CTL; epitope; PRRSV; vaccine

期刊名称：FRONTIERS IN IMMUNOLOGY （ 影响因子：7.561； 五年影响因子：7.624 ）

ISSN： 1664-3224

年卷期： 2020 年 10 卷

页码：

收录情况： SCI

摘要： 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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