Differential processing and presentation of the H-2D(b)-restricted epitope from two different strains of influenza virus nucleoprotein.
The influenza virus strains A/NT/60/68 and A/PR/8/34 both have an immunodominant D(b)-restricted epitope in their nucleoprotein (NP) at amino acid residues 366-374, with two amino acid differences between the epitopes. Cross-reactive cytotoxic T lymphocytes (CTLs) were generated by priming mice with the influenza virus A/NT/60/68 NP and restimulating in vitro with influenza virus A/PR/8/34. CTLs that gave high levels of specific lysis recognized target cells infected with either strain of influenza virus with similar efficiency. Surprisingly, when target cells were infected with recombinant vaccinia viruses (VV) expressing the two different NPs, presentation of the D(b)-restricted epitope from the A/NT/60/68 NP was extremely poor, whereas presentation of the equivalent epitope from the A/PR/8/34 NP was as efficient as in influenza virus-infected cells. This difference was observed in spite of the fact that the two NP sequences show 94% identity at the amino acid sequence level. Experiments with additional cross-reactive CTL cell lines which recognized target cells less efficiently revealed a similar difference in presentation between the two NP epitopes in influenza virus-infected cells and showed a difference in the efficiency of presentation of the D(b)-restricted epitope from the two NP molecules independent of VV infection. The results show that two equivalent epitopes in highly similar proteins are processed with very different efficiency, even though they are both immunodominant epitopes. They also suggest that the previously described inhibition of antigen presentation by VV is a general, non-specific effect, which is more apparent for epitopes that are processed and presented less efficiently.
Potter
Paul
P
Department of Immunology, Imperial College School of Medicine (St Mary's Campus), Norfolk Place, London W2 1PG, UK1.
Tourdot
Sophie
S
Department of Immunology, Imperial College School of Medicine (St Mary's Campus), Norfolk Place, London W2 1PG, UK1.
Blanchard
Tom
T
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK2.
Smith
Geoffrey L
GL
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK2.
Gould
Keith G
KG
Department of Immunology, Imperial College School of Medicine (St Mary's Campus), Norfolk Place, London W2 1PG, UK1.
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D002460:Cell Line; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009698:Nucleoproteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D009698:Nucleoproteins; D010446:Peptide Fragments; D014758:Viral Core Proteins; C102366:nucleoprotein (366-374), influenza virus