Publication: Exogenous, TAP-independent lysosomal presentation of a respiratory syncytial virus CTL epitope.
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2012-11
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Wiley
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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.
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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
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Immunol Cell Biol . 2012 Nov;90(10):978-82.