Overlapping epitopes that are recognized by CD8+ HLA class I-restricted and CD4+ class II-restricted cytotoxic T lymphocytes are contained within an influenza nucleoprotein peptide.
Viral epitopes that are recognized by both HLA class I-restricted and class II-restricted T cells have been defined for a type A influenza virus nucleoprotein (NP) peptide. CD8+ and CD4+ CTL lines have been generated against a synthetic peptide encompassing residues 335 to 349 of NP that are restricted by HLA-B37 and HLA-DQw5, respectively. Both of these CTL populations were capable of specifically lysing influenza A virus-infected targets, indicating that a naturally processed NP peptide(s) was being mimicked by the NP (335-349) peptide. Amino acid residues that are critical for recognition of this NP determinant in the context of HLA-B37 and HLA-DQw5 were investigated by the use of panels of truncated and alanine-substituted NP peptides. The results demonstrate that: 1) truncations in the amino- or carboxy-terminal ends differentially affect CD8+ and CD4+ CTL recognition; 2) the NP (335-349) sequence contains two octapeptide epitopes that share a core of six amino acid residues (NP 338-343); and 3) alanine substitutions at five of these residues abrogated recognition by at least one of the CD8+ and CD4+ CTL lines. Thus, these class I- and class II-restricted CTL lines recognize similar but distinct epitopes, and different structural features of the NP peptide are required for presentation by HLA-B37 and HLA-DQw5. Comparison of the amino acid sequences of the NP peptide presented by HLA-B37 and HLA-DQw5 with other peptides known to be presented by both class I and class II molecules revealed a common motif among these peptides.
Molecular Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
B M
BM
Carreno
R V
RV
Turner
W E
WE
Biddison
J E
JE
Coligan
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D006681:HLA-D Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology*; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000737:chemistry / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000737:chemistry / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology
D016827:CD8 Antigens; D000939:Epitopes; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D014758:Viral Core Proteins; D014764:Viral Proteins