Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation

Science. 2007 Apr 27;316(5824):612-6. doi: 10.1126/science.1137971.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / immunology
  • Endocytosis
  • Endosomes / immunology
  • Endosomes / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Lectins, C-Type / metabolism
  • Lymphocyte Activation*
  • Lysosomes / immunology
  • Lysosomes / metabolism
  • Macrophages / immunology
  • Mannose-Binding Lectins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Models, Immunological
  • Ovalbumin / immunology
  • Pinocytosis
  • Receptors, Cell Surface / metabolism
  • Receptors, Scavenger / metabolism

Substances

  • Antigens
  • Histocompatibility Antigens Class II
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Receptors, Scavenger
  • mannose receptor
  • Ovalbumin