HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs.
The potential value of peptide binding motifs of HLA class I molecules for the prediction of viral epitopes presented to T cells has been analyzed for two common HLA alleles. CTL generated against type A influenza virus recognize peptide epitopes derived from the nucleoprotein (NP) and basic polymerase 1 presented by HLA-A1, and epitopes derived from NP presented by HLA-A3. Distinct peptide binding motifs with characteristic anchor residues were previously identified for each of these class I molecules based on the sequences of endogenous peptides: for HLA-A1, position 3 = Asp or Glu and position 9 = Tyr; for HLA-A3, position 2 = Leu and position 9 = Lys or Tyr. Six peptides containing the HLA-A1 binding motif were identified within the sequences of the NP and basic polymerase 1 proteins, and one peptide containing the HLA-A3 motif was identified in the NP molecule. Three of the six HLA-A1 peptides and the one HLA-A3 NP peptide could bind to HLA-A1 or HLA-A3, respectively, in an in vitro peptide binding assay. Two of the HLA-A1-binding peptides could sensitize target cells for lysis by influenza virus-immune CTL populations restricted by HLA-A1 (NP 44-52 CTELKLSDY and PB1 591-599 VSDGGPNLY), and the one HLA-A3 NP peptide (NP 265-273 ILRGSVAHK) could sensitize target cells for lysis by HLA-A3-restricted influenza-immune CTL. Each peptide was also shown to be able to induce peptide-specific class I-restricted CTL in vitro, and the CTL generated against two of these peptides could specifically recognize virus-infected targets. Thus, these peptide binding motifs can be used to construct immunogenic synthetic epitopes which are capable of inducing antiviral T cell-mediated immune responses.
DiBrino
M
M
Biological Resources Branch, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892.
Tsuchida
T
T
Turner
R V
RV
Parker
K C
KC
Coligan
J E
JE
Biddison
W E
WE
D000595:Amino Acid Sequence; D001665:Binding Sites; D000939:Epitopes; D015788:HLA-A1 Antigen / Q000276:immunology*; D015791:HLA-A3 Antigen / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology*; D009975:Orthomyxoviridae / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D000939:Epitopes; D015788:HLA-A1 Antigen; D015791:HLA-A3 Antigen; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1