Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation.
The mechanisms that allow antigen-presenting cells (APCs) to selectively present extracellular antigen to CD8+ effector T cells (cross-presentation) or to CD4+ T helper cells are not fully resolved. We demonstrated that APCs use distinct endocytosis mechanisms to simultaneously introduce soluble antigen into separate intracellular compartments, which were dedicated to presentation to CD8+ or CD4+ T cells. Specifically, the mannose receptor supplied an early endosomal compartment distinct from lysosomes, which was committed to cross-presentation. These findings imply that antigen does not require intracellular diversion to access the cross-presentation pathway, because it can enter the pathway already during endocytosis.
Burgdorf
Sven
S
Institute of Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms-Universität, Bonn, Germany. sven.burgdorf@ukb.uni-bonn.de
Kautz
Andreas
A
Böhnert
Volker
V
Knolle
Percy A
PA
Kurts
Christian
C
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004705:Endocytosis; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D010047:Ovalbumin / Q000276:immunology; D010873:Pinocytosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism
D000941:Antigens; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D010047:Ovalbumin