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HLA B8-restricted cytotoxic T lymphocytes (CTL) specific for influenza A virus were generated and shown to recognize the nucleoprotein (NP). The dominant epitope was mapped using recombinant vaccinia viruses that expressed fragments of the NP and then synthetic peptides based on the NP amino acid sequence. The peptide 380-393 was first identified and further refined; it was shown that the glutamic acid at position 380 was essential for recognition by CTL and that the nonamer 380-388 was the optimum peptide. Six HLA B8-positive influenza immune donors that we have tested respond to this peptide as part of their influenza-specific CTL response. The amino acid sequence of the peptide epitope was compared to six other known virus peptides known to be restricted by HLA B8 and a sequence homology was identified, which predicted nonamer and octamer epitope sequences. Probable anchor residues were identified at peptide residues 3 (lysine/arginine), 5 (lysine/arginine) and 9 (leucine/isoleucine). Support for this pattern came from sequencing peptides eluted from purified HLA B8 molecules, where lysines were predominant at positions 3 and 5. One of the predicted epitope peptides was made and shown to be recognized by specific CTL. These and the two others were shown to compete with NP 380-388 for binding to HLA B8. A model was made of the HLA B8 molecule and negatively charged pockets predicted, which could accommodate the positively charged side chains of the peptide anchor residues.

Original publication

DOI

10.1002/eji.1830230222

Type

Journal article

Journal

Eur J Immunol

Publication Date

02/1993

Volume

23

Pages

447 - 453

Keywords

Amino Acid Sequence, Antigen-Presenting Cells, Epitopes, Gene Expression, HIV Infections, HIV-1, HLA-B8 Antigen, Humans, Influenza A virus, Molecular Sequence Data, Nucleoproteins, Peptides, Protein Conformation, RNA-Binding Proteins, Structure-Activity Relationship, T-Lymphocytes, Cytotoxic, Viral Core Proteins, Viral Vaccines