期刊
IMMUNOLOGY AND CELL BIOLOGY
卷 94, 期 10, 页码 964-974出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/icb.2016.59
关键词
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资金
- National Health and Medical Research Council (NH&MRC) Senior Principal Research Fellowships
- NH&MRC Early Career Research Fellowship
Cross-presentation of exogenous protein antigens by B cells through the major histocompatibility complex ( MHC) class I pathway in lymphoid malignancies, and transplant setting has been recognised as an important mediator of immune pathogenesis and T cell-mediated immune regulation. However, the precise mechanism of cross-presentation of exogenous antigens in B cells has remained unresolved. Here we have delineated a novel pathway for cross-presentation in B cells, which involves synergistic cooperation of the proteasome and autophagy. After endocytosis, protein antigen is processed through an autophagy-and proteasome-dependent pathway and CD8(+) T-cell epitopes are loaded onto MHC class I molecules within the autophagolysomal compartment rather than the conventional secretory pathway, which requires transporters associated with antigen processing-dependent transport. Interestingly, this cross-presentation was critically dependent on valosin-containing protein ( VCP)/p97 ATPase through its participation in autophagy. Loss of VCP/p97 ATPase was coincident with accumulation of LC3-II and marked reduction in antigen presentation. These observations provide unique insight on how the autophagy and proteasomal degradation systems interconnect to coordinate MHC class I-restricted cross-presentation in B cells.
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