論文 - 詳細
| RRC ID | 72391 |
|---|---|
| 著者 | Misumi S, Nakajima R, Takamune N, Shoji S. |
| タイトル | A cyclic dodecapeptide-multiple-antigen peptide conjugate from the undecapeptidyl arch (from Arg(168) to Cys(178)) of extracellular loop 2 in CCR5 as a novel human immunodeficiency virus type 1 vaccine. |
| ジャーナル | J Virol |
| Abstract |
A cyclic closed-chain dodecapeptide (cDDR5) mimicking the conformation-specific domain of CCR5 was prepared in which Gly-Asp, as a dipeptide forming a spacer arm, links the amino and carboxyl termini of the decapeptidyl linear chain (Arg(168) to Thr(177)) derived from the undecapeptidyl arch (UPA; Arg(168) to Cys(178)) of extracellular loop 2 (ECL2) in CCR5. Novel monoclonal antibodies were raised against cDDR5 conjugated with a multiple-antigen peptide (cDDR5-MAP), and the purified antibody [KB8C12, immunoglobulin M(kappa)] reacted with cDDR5, but not with linear DDR5, in real-time biomolecular interaction analysis using surface plasmon resonance. The antibody also reacted with cells expressing CCR5, but not with cells expressing CXCR4, and the immunoreaction was competed by cDDR5-MAP. The antibody significantly interfered with chemotaxis induced by macrophage inflammatory protein, 1beta, and at a concentration of 1.67 nM it almost completely inhibited infection by human immunodeficiency virus type 1 (HIV-1) R5, but not by HIV-1 X4, as observed by use of a new phenotypic assay for drug susceptibility of HIV-1 using the CCR5-expressing HeLa CD4(+) cell clone 1-10 (MAGIC-5). Furthermore, cDDR5-MAP suppressed infection by HIV-1 R5 at relatively high concentrations (50 to 400 microM) in a dose-dependent manner but did not suppress infection by HIV-1 X4. Taken together, these results indicate that the antibody is conformation specific and recognizes the conformation-specific domain of the UPA of ECL2. Moreover, both the antibody and its immunogen, the cDDR5-MAP conjugate, may be useful in developing a new candidate vaccine for HIV therapy. |
| 巻・号 | 75(23) |
| ページ | 11614-20 |
| 公開日 | 2001-12-1 |
| DOI | 10.1128/JVI.75.23.11614-11620.2001 |
| PMID | 11689643 |
| PMC | PMC114748 |
| MeSH | AIDS Vaccines / chemistry AIDS Vaccines / immunology* Antibodies, Monoclonal / immunology Antibody Specificity Arginine / chemistry* Chemokine CCL4 Chemotaxis / drug effects Cysteine / chemistry* Flow Cytometry HIV Antigens / chemistry HIV Antigens / immunology* HIV-1 / immunology* HIV-1 / physiology HeLa Cells Humans Macrophage Inflammatory Proteins / pharmacology Membrane Fusion / immunology Oligopeptides / chemistry Oligopeptides / immunology* Receptors, CCR5 / chemistry Receptors, CCR5 / immunology* Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization |
| IF | 4.501 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |