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Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells

Nature Immunology volume 6, pages 107–113 (2005)Cite this article

Abstract

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.

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Figure 1: Effects of soluble US6(20–146) on the surface expression of MHC class I molecules.
Figure 2: Exogenous soluble US6(20–146) inhibits ER-based translocation by TAP.
Figure 3: DCs but not macrophages accumulate US6 after its internalization.
Figure 4: Exogenous β2M reaches the ER lumen in DCs from β2M-deficient mice.
Figure 5: Exogenous human β2M interacts functionally with MHC class I heavy chains in the ER of mouse DCs.
Figure 6: Exogenous US6(20–146) inhibits endogenous antigen presentation.

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Acknowledgements

Supported by the Howard Hughes Medical Institute and National Institutes of Health (F31 AI 101347 to A.L.A.).

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Yale University School of Medicine, Section of Immunobiology, New Haven, 06520, Connecticut, USA

    Anne L Ackerman & Peter Cresswell

  2. Institut für Biochemie, Johann Wolfgang Goethe Universität, Frankfurt, 60439, Germany

    Christoph Kyritsis & Robert Tampé

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  1. Anne L Ackerman
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Correspondence to Peter Cresswell.

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Ackerman, A., Kyritsis, C., Tampé, R. et al. Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells. Nat Immunol 6, 107–113 (2005). https://doi.org/10.1038/ni1147

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