title: Exogenous, TAP-independent lysosomal presentation of a respiratory syncytial virus CTL epitope.
abstract: Respiratory syncytial virus causes lower respiratory tract infections in infancy and old age, affecting also immunocompromised patients. The viral fusion protein is an important vaccine candidate eliciting antibody and cell-mediated immune responses. CD8(+) cytotoxic T lymphocytes (CTLs) are known to have a role in both lung pathology and viral clearance. In BALB/c mice, the fusion protein epitope F249-258 is presented to CTLs by the murine major histocompatibility complex (MHC) class I molecule K(d). In cells infected with recombinant vaccinia viruses encoding the fusion protein, F249-258 is presented by MHC class I molecules through pathways that are independent of the transporters associated with antigen processing (TAP). We have now found that F249-258 can be generated from non-infectious virus from an exogenous source. Antigen processing follows a lysosomal pathway that appears to require autophagy. As a practical consequence, inactivated virus suffices for in vivo priming of virus-specific CTLs.
authors.affiliation: Inmunología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Johnstone
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramos
authors.forename: Blanca
authors.initials: B
authors.lastname: García-Barreno
authors.forename: Daniel
authors.initials: D
authors.lastname: López
authors.forename: José A
authors.initials: JA
authors.lastname: Melero
authors.forename: Margarita
authors.initials: M
authors.lastname: Del Val
mesh_terms: D000368:Aged; D000818:Animals; D017951:Antigen Presentation; D000950:Antigens, Ly / Q000378:metabolism; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001343:Autophagy; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D008247:Lysosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines