title: A broad cytotoxic T lymphocyte response to influenza type B virus presented by multiple HLA molecules.
abstract: The HLA restriction and epitope specificity of cytotoxic T lymphocytes (CTL) involved in recovery from influenza type B infection have not been extensively characterized. Here lymphocytes obtained from a healthy individual contained virus-specific CTL restricted by class I HLA molecules, HLA-A1, A2, B7 and B8, and the class II HLA molecules, HLA-DR1 and DR3. Four conserved viral epitopes were predicted from allele-specific motifs for peptides interacting with HLA-B8 and HLA-DR1. Bulk CTL recognized three 9mer HLA-B8-restricted peptides from nucleoprotein, residues 30-38, 263-271 and 413-421, and a 13mer HLA-DR1-restricted peptide from hemagglutinin, residues 308-320. The epitopes presented by HLA-A1, HLA-B7 and HLA-DR3 remain undefined. Peptide-specific CTL lines recognized influenza type B virus-infected cells indicating the peptides are representative of naturally processed epitopes. A hemagglutinin peptide-specific CD4 CTL clone expressed approximately 200 molecules of perforin mRNA/cell, suggestive of a functional perforin pathway for target cell lysis. The results indicate a broad CTL response composed of both CD8 CTL and CD4 CTL recognizing viral epitopes presented by multiple HLA molecules.
authors.affiliation: Center for Biologics Evaluation and Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Robbins
authors.forename: P A
authors.initials: PA
authors.lastname: Rota
authors.forename: S Z
authors.initials: SZ
authors.lastname: Shapiro
mesh_terms: D017951:Antigen Presentation; D017124:Conserved Sequence; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D006680:HLA Antigens / Q000378:metabolism*; D015788:HLA-A1 Antigen / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000378:metabolism; D015793:HLA-B7 Antigen / Q000378:metabolism; D015795:HLA-B8 Antigen / Q000378:metabolism; D015236:HLA-C Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D009981:Influenza B virus / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen; D015793:HLA-B7 Antigen; D015795:HLA-B8 Antigen; D015236:HLA-C Antigens; C040178:HLA-C*70 antigen; D006684:HLA-DR Antigens; D012333:RNA, Messenger