title: Antigen processing for MHC class I restricted presentation of exogenous influenza A virus nucleoprotein by B-lymphoblastoid cells.
abstract: In general, exogenous proteins are processed by antigen-presenting cells in the endosomes for major histocompatibility complex (MHC) class II presentation to CD4+ T cells, while proteins synthesized endogenously are processed in the cytoplasm for MHC class I presentation to CD8+ T cells. However, it is recognized that exogenous proteins can be processed for MHC class I presentation also, and evidence in favour of alternatives to the conventional MHC class I processing and presentation pathway is accumulating. Here, we show that exogenous recombinant influenza A virus nucleoprotein (rNP) is processed for MHC class I presentation to CD8+ cytotoxic T lymphocytes (CTL) by EBV-transformed, B-lymphoblastoid cell lines (B-LCL). Processing of rNP for HLA-B27-associated presentation seemed to follow the conventional MHC class I pathway predominantly, as presentation was diminished in the presence of lactacystin and brefeldin A, but was less sensitive to chloroquine and NH4Cl. HLA-B27-associated presentation was also observed using cells lacking a functional transporter associated with antigen processing, suggesting that alternative pathways may be exploited for processing of rNP.
authors.affiliation: Institute of Virology and WHO National Influenza Centre, Erasmus Medical Centre Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: J T
authors.initials: JT
authors.lastname: Voeten
authors.forename: G F
authors.initials: GF
authors.lastname: Rimmelzwaan
authors.forename: N J
authors.initials: NJ
authors.lastname: Nieuwkoop
authors.forename: R A
authors.initials: RA
authors.lastname: Fouchier
authors.forename: A D
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D020126:Brefeldin A / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D011992:Endosomes / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D008285:Major Histocompatibility Complex; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins / Q000276:immunology*
chemical_list: D004791:Enzyme Inhibitors; D015395:Histocompatibility Antigens Class I; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; C067713:lactacystin; D020126:Brefeldin A; D002738:Chloroquine; D000111:Acetylcysteine