Exogenous, TAP-independent lysosomal presentation of a respiratory syncytial virus CTL epitope.

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 t...

Descripción completa

Detalles Bibliográficos
Autores: Ramos, Manuel, Garcia-Barreno, Blanca, Lopez, Daniel, Melero, Jose Antonio, Val, Margarita del, Johnstone, Carolina
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/10633
Acceso en línea:http://hdl.handle.net/20.500.12105/10633
Access Level:acceso abierto
Palabra clave:Antigen Presentation
Aged
Animals
Antigens, Ly
Antigens, Viral
Autophagy
Cell Line
Epitopes, T-Lymphocyte
Histocompatibility Antigens Class I
Humans
Immunocompromised Host
Infant
Lysosomes
Membrane Proteins
Mice
Mice, Inbred BALB C
Peptide Fragments
Recombinant Fusion Proteins
Respiratory Syncytial Virus Infections
Respiratory Syncytial Viruses
T-Lymphocytes, Cytotoxic
Viral Vaccines
Descripción
Sumario: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.