Egress of internalized antigen into cytosol from early endosome

Stable Identifier
R-HSA-1236968
Type
Reaction [BlackBoxEvent]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

Endocytosed antigens must leave the endocytic structure to enter into the MHC I pathway before exhaustive degradation within lysosomes. The canonical pathway is the transporter associated with antigen processing (TAP)-dependent cytosolic pathway, which involves the translocation of endocytosed antigens into the cytosol where they are degraded into antigenic peptides by the proteasome and transported to ER through TAP. This hypothesis comes from indirect evidences showing that proteasome inhibitors block cross presentation of certain antigens (Amigorena et al. 2010, Burgdorf et al. 2008) . According to this model antigens are translocated into the cytosol by an undefined mechanism.
There are less well-characterized mechanisms for the delivery of exogenous antigens into the cytosol. Certain peptides with highly positively charged sequences derived from HIV tat protein or the Antennapedia homeodomain (AntHD) protein seem to penetrate into the cytosol directly across the plasma membrane (Monu et al. 2007, Vendeville et al. 2004). It is also proposed that some exogenous antigens can be exchanged between neighboring cells through gap junctions, leading to cross presentation by the recipient cell (Monu et al. 2007, Neijssen et al. 2005).
Once internalized antigens are routed into the cytosol, they follow the conventional pathway of proteasome digestion and TAP mediated transport of peptides into the ER lumen.

Literature References
PubMed ID Title Journal Year
10559964 Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells

Rodriguez, A, Regnault, A, Kleijmeer, M, Ricciardi-Castagnoli, P, Amigorena, S

Nat Cell Biol 1999
16530046 Ligands for clathrin-mediated endocytosis are differentially sorted into distinct populations of early endosomes

Lakadamyali, M, Rust, MJ, Zhuang, X

Cell 2006
9257826 Introduction of soluble proteins into the MHC class I pathway by conjugation to an HIV tat peptide

Kim, DT, Mitchell, DJ, Brockstedt, DG, Fong, L, Nolan, GP, Fathman, CG, Engleman, EG, Rothbard, JB

J Immunol 1997
15761154 Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate

Delamarre, L, Pack, M, Chang, H, Mellman, I, Trombetta, ES

Science 2005
15020715 HIV-1 Tat enters T cells using coated pits before translocating from acidified endosomes and eliciting biological responses

Vendeville, A, Rayne, F, Bonhoure, A, Bettache, N, Montcourrier, P, Beaumelle, B

Mol Biol Cell 2004
15592474 Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells

Ackerman, AL, Kyritsis, C, Tampé, R, Cresswell, P

Nat Immunol 2005
9022030 Constitutive macropinocytosis allows TAP-dependent major histocompatibility complex class I presentation of exogenous soluble antigen by bone marrow-derived dendritic cells

Norbury, CC, Chambers, BJ, Prescott, AR, Ljunggren, HG, Watts, C

Eur J Immunol 1997
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