5ylx
From Proteopedia
Integrated illustration of a valid epitope based on the SLA class I structure and tetramer technique could carry forward the development of molecular vaccine in swine species
Structural highlights
FunctionPublication Abstract from PubMedTo 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. Illumination 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 Front Immunol. 2020 Jan 8;10:2995. doi: 10.3389/fimmu.2019.02995. eCollection, 2019. PMID:31969884[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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