Autophagy mediates transporter associated with antigen processing-independent presentation of viral epitopes through MHC class I pathway.
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.
Australian Centre for Vaccine Development and Tumour Immunology Laboratory, Division of Immunology, Queensland Institute of Medical Research, Brisbane, Australia.
Siok-Keen
SK
Tey
Rajiv
R
Khanna
D018528:ATP-Binding Cassette Transporters / Q000276:immunology* / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000502:physiology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000071192:Autophagy-Related Protein 12; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D025841:Small Ubiquitin-Related Modifier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C466624:ATG12 protein, human; D018528:ATP-Binding Cassette Transporters; D000956:Antigens, Viral; D000071192:Autophagy-Related Protein 12; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D034741:RNA, Small Interfering; D025841:Small Ubiquitin-Related Modifier Proteins; C477327:transporter associated with antigen processing (TAP)