Characterization of an overlapping CD8+ and CD4+ T-cell epitope on rubella capsid protein.
A synthetic peptide corresponding to rubella virus capsid protein residues 263 to 275 which contains an epitope recognized by a cloned CD4+ cytotoxic T-lymphocyte (CTL) line was used to induce CD8+ T-cell lines specific to this peptide. A peptide-specific CD8+ CTL clone was derived and characterized. This peptide-specific CD8+ CTL clone exhibited cytotoxicity against target cells infected by a vaccinia recombinant virus expressing rubella virus capsid protein, but not by target cells infected by vaccinia recombinant virus expressing rubella virus E1 or E2 envelope proteins. Analysis of HLA class I restriction of the CD8+ CTL clone revealed that A11 and A3 were restrictive elements. Fine mapping with truncated and overlapping peptide analogs revealed a nonamer sequence, C(264-272), as the T-cell epitope eliciting stronger cytotoxicity. Two anchor residues for binding to HLA A11 and A3 were identified at position 2 (isoleucine) and at position 9 (histidine) or at position 8 (arginine) of the epitope sequence. The identification of overlapping CD4+ and CD8+ T-cell epitopes within the capsid protein sequence C(263-275) implicates a strategy for using such epitopes in a candidate peptide-based rubella vaccine.
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Faculty of Medicine, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia, V5Z 4H4, Canada.
Mitchell
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Décarie
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Gillam
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Tingle
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D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology; D012412:Rubella virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D015704:CD4 Antigens; D016827:CD8 Antigens; D006680:HLA Antigens; D010446:Peptide Fragments