Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells.
In dendritic cells (DCs), peptides derived from internalized particulate substrates are efficiently cross-presented by major histocompatibility complex (MHC) class I molecules. Exogenous soluble antigens are also presented by DCs but with substantially lower efficiency. Here we show that particulate and soluble antigens use different transport pathways. Particulate antigens have been shown to access peripheral endoplasmic reticulum (ER)-like phagosomes that are competent for cross-presentation, whereas we show here that soluble proteins that escape proteolysis enter the lumen of the ER. From there, they may be translocated into the cytosol by the pathway established for ER-associated degradation and their derived peptides may be transported back into the ER for binding by MHC class I molecules. MHC class I presentation involving the constitutive retrograde transport of soluble proteins to the ER by DCs may facilitate DC tolerance to components of their extracellular environment.
Ackerman
Anne L
AL
Howard Hughes Medical Institute, Yale University School of Medicine, Section of Immunobiology, New Haven, Connecticut 06520, USA.
Kyritsis
Christoph
C
Tampé
Robert
R
Cresswell
Peter
P
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000276:immunology* / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I