Autophagy mediates transporter associated with antigen processing-independent presentation of viral epitopes through MHC class I pathway.

Abstract:

:The endogenous presentation of the majority of viral epitopes through MHC class I pathway is strictly dependent on the transporter associated with antigen processing (TAP) complex, which transfers the peptide products of proteasomal degradation into the endoplasmic reticulum. A small number of epitopes can be presented through the TAP-independent pathway, the precise mechanism for which remains largely unresolved. Here we show that TAP-independent presentation can be mediated by autophagy and that this process uses the vacuolar pathway and not the conventional secretory pathway. After macroautophagy, the antigen is processed through a proteasome-independent pathway, and the peptide epitopes are loaded within the autophagolysosomal compartment in a process facilitated by the relative acid stability of the peptide-MHC interaction. Despite bypassing much of the conventional MHC class I pathway, the autophagy-mediated pathway generates the same epitope as that generated through the conventional pathway and thus may have a role in circumventing viral immune evasion strategies that primarily target the conventional pathway.

journal_name

Blood

journal_title

Blood

authors

Tey SK,Khanna R

doi

10.1182/blood-2012-01-402404

subject

Has Abstract

pub_date

2012-08-02 00:00:00

pages

994-1004

issue

5

eissn

0006-4971

issn

1528-0020

pii

blood-2012-01-402404

journal_volume

120

pub_type

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