Regulation of antigen transport into the cytosol for cross-presentation by ubiquitination of the mannose receptor

• Published in: Molecular immunology Vol. 55; no. 2; pp. 146 - 148
• Main Authors: Zehner, Matthias, Burgdorf, Sven
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2013
• Subjects: Antigen Presentation; Cross-presentation; Cross-Priming; Cytosol - immunology; Cytosol - metabolism; Dendritic cells; Dendritic Cells - immunology; DNA-Binding Proteins - metabolism; Endocytosis; Endosomal Sorting Complexes Required for Transport - metabolism; Endosomes - immunology; Histocompatibility Antigens Class I - immunology; Humans; Lectins, C-Type - metabolism; Mannose-Binding Lectins - metabolism; Nuclear Proteins - metabolism; Protein Transport; Receptors, Cell Surface - metabolism; Transcription Factors - metabolism; Ubiquitination; Cross-presentation; Dendritic cells; Endocytosis
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2012.10.010

► Ubiquitination of the MR is essential for cross-presentation. ► p97 recruitment by poly-ubiquitination of the mannose receptor. ► Regulation of MR ubiquitination by TSG101. The molecular mechanisms governing cross-presentation of extracellular antigens on MHC I molecules are not fully understood. It is generally assumed that, in order to be processed for cross-presentation, most antigens need to be transported from the endosomal compartment into the cytosol to be processed by the cytosolic proteasome. The mechanisms regulating such intracellular transport are largely unknown. In a recent study, we demonstrated that the ubiquitination status of the mannose receptor (MR), an endocytic receptor that targets its ligands specifically toward cross-presentation, can regulate such antigen export into the cytosol. Poly-ubiquitination of the MR recruits p97 toward the endosomal membrane, which is essential for antigen translocation out of the endosomes. Furthermore, we identified Tumor Susceptibility Gene 101 (TSG101) as an important regulator of MR poly-ubiquitination and hence of antigen translocation and cross-presentation. Additionally, we describe in this article some perspectives and open questions regarding the molecular mechanisms of cross-presentation. In particular, we highlight the search for proteins regulating antigen translocation in the cytosol, the recruitment of ER proteins and proteasomes toward antigen-containing endosomes and the importance of antigen stability for cross-presentation.