A dominant Th epitope in influenza nucleoprotein. Analysis of the fine specificity and functional repertoire of T cells recognizing a single determinant.
The sequence 260-283 of the nucleoprotein (NP) of influenza A virus is an epitope recognized by virus-immune lymph node cells from CBA (H-2k), B6 (H-2b), and B10.S (H-2s) mice. Further analysis shows that there are at least two Th epitopes within this sequence: the one close to the N-terminal (p260-273) is recognized by T cells from CBA and B6 mice while that close to the carboxyl-terminal (p270-283) is a dominant Th determinant in B10.S mice. The fine specificity of the recognition of this epitope by NP-specific T cell clones is also studied. When B10.S mice were infected intranasally or i.v. with live influenza virus, or immunized by different ways with various Ag preparations, P270-283 persistently emerged as a dominant T cell epitope. Immunization of B10.S mice with peptide p270-283 induces T cells with different in vivo functions including class II-restricted cytotoxicity, cognate help for Ag-specific antibody synthesis and delayed type hypersensitivity. This may have important implications for the understanding of the differentiation and classification of subsets of CD4+ T cells. The corresponding sequence of the NP of an equine influenza virus, A/Eq/Prague/56, which has a substitution (leucine to proline) at position 283, was not recognized by the lymph node cells from mice primed with either A/Okuda or A/Eq/Prague. However, the peptide, p270-283(E), representing this sequence induced T cell responses to both human and equine viruses. The data are discussed with respect to the development of viral vaccines.
Department of Experimental Immunobiology, Wellcome Biotechnology, Beckenham, UK.
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D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells; D000939:Epitopes; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007377:Interleukin-3 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology; D011392:Proline; D011487:Protein Conformation; D016601:RNA-Binding Proteins; D011863:Radioimmunoassay; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013997:Time Factors; D014758:Viral Core Proteins; D014764:Viral Proteins / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D007377:Interleukin-3; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D009842:Oligopeptides; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins; D011392:Proline