title: Relevance of viral context and diversity of antigen-processing routes for respiratory syncytial virus cytotoxic T-lymphocyte epitopes.
abstract: Antigen processing of respiratory syncytial virus (RSV) fusion (F) protein epitopes F85-93 and F249-258 presented to cytotoxic T-lymphocytes (CTLs) by the murine major histocompatibility complex (MHC) class I molecule Kd was studied in different viral contexts. Epitope F85-93 was presented through a classical endogenous pathway dependent on the transporters associated with antigen processing (TAP) when the F protein was expressed from either RSV or recombinant vaccinia virus (rVACV). At least in cells infected with rVACV encoding either natural or cytosolic F protein, the proteasome was required for epitope processing. In cells infected with rVACV encoding the natural F protein, an additional endogenous TAP-independent presentation pathway was found for F85-93. In contrast, epitope F249-258 was presented only through TAP-independent pathways, but presentation was brefeldin A sensitive when the F protein was expressed from RSV, or mostly resistant when expressed from rVACV. Therefore, antigen-processing pathways with different mechanisms and subcellular localizations are accessible to individual epitopes presented by the same MHC class I molecule and processed from the same protein but in different viral contexts. This underscores both the diversity of pathways available and the influence of virus infection on presentation of epitopes to CTLs.
authors.affiliation: Unidad de Inmunología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Pozuelo km 2, E-28220 Majadahonda, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Johnstone
authors.affiliation: Unidad de Inmunología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Pozuelo km 2, E-28220 Majadahonda, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Guil
authors.affiliation: Unidad de Proteómica, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Pozuelo km 2, E-28220 Majadahonda, Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rico
authors.affiliation: Unidad de Biología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Pozuelo km 2, E-28220 Majadahonda, Madrid, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: García-Barreno
authors.affiliation: Unidad de Proteómica, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Pozuelo km 2, E-28220 Majadahonda, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: López
authors.affiliation: Unidad de Biología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Pozuelo km 2, E-28220 Majadahonda, Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Melero
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC/Universidad Autónoma de Madrid, E-28049 Madrid, Spain.|Unidad de Inmunología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Pozuelo km 2, E-28220 Majadahonda, Madrid, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Del Val