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| Article Authors: | S Man; M H Newberg; V L Crotzer; C J Luckey; N S Williams; Y Chen; E L Huczko; J P Ridge; V H Engelhard |
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| Article Title: | Definition of a human T cell epitope from influenza A non-structural protein 1 using HLA-A2.1 transgenic mice. |
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| Reference ID: | 315054 |
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| Abstract: | Previous results from this laboratory demonstrated that the dominant influenza A epitope recognized by HLA-A2.1-restricted cytotoxic T lymphocytes (CTL) from HLA-A2.1 transgenic mice was the matrix protein 1 (M1) peptide epitope that is immunodominant in human CTL responses. However, analysis of a large number of CTL lines revealed a subset of influenza A/PR/8/34-specific murine CTL that recognized an HLA-A2.1-restricted epitope distinct from M1. Using recombinant vaccinia viruses encoding different influenza gene segments, the epitope recognized by these CTL was shown to be derived from A/PR/8 non-structural protein 1 (NS1). Because these CTL did not recognize targets infected with the A/Alaska/6/77 strain of influenza, candidate peptide epitopes were synthesized based on sequences that included an HLA-A2.1-specific binding motif, and that differed between A/PR/8 and A/Alaska. All of these CTL recognized a nonamer and a decamer peptide which contained a common eight amino acid sequence and two distinct sets of binding motif residues. However, the nonamer peptide was able to sensitize CTL for half-maximal lysis at 80- to 2500-fold lower doses than either the octamer or decamer. The homologous peptide derived from A/Alaska NS1 contained conservative amino acid changes at positions 4 and 8, and was not recognized at any tested concentration, although it bound with higher affinity to HLA-A2.1 than the peptide from A/PR/8. The A/PR/8 NS1 nonamer epitope was also recognized by human influenza A-specific CTL derived from two individuals. These results substantiate the general utility of HLA class I transgenic mice for the identification of human CTL epitopes for other pathogens. |
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| Affiliations: | Department of Microbiology, University of Virginia, Charlottesville 22908, USA. |
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| Date: | 1995 |
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| Reference Type: | Literature |
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| PubMed ID: | 7547687 |
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| Journal: | Int Immunol |
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| Journal Volume: | 7 |
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| Article Pages: | 597-605 |
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| Journal ISSN: | 1460-2377 |
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| Article Chemical List: | HLA-A2 Antigen;INS1 protein, influenza virus;Immunodominant Epitopes;Peptides;Viral Nonstructural Proteins |
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| Article MeSH List: | Amino Acid Sequence; Animals; HLA-A2 Antigen(genetics; immunology); Humans; Immunodominant Epitopes(immunology); Influenza A virus(immunology); Mice; Mice, Transgenic(immunology); Molecular Sequence Data; Peptides(immunology); T-Lymphocytes, Cytotoxic(immunology); Viral Nonstructural Proteins(analysis; immunology) |
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| Article Comments: | Data originally imported from the Database of Functional Molecular Immunology, FIMM (http://sdmc.lit.org.sg:8080/fimm/) and from the HLA Ligand Database (http://hlaligand.ouhsc.edu/) |
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| Curation Last Updated: | 2011-11-04 20:01:53 |
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