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Antigen Presentation

Direct Antigen Presentation

  • Dendritic cells, monocytes, macrophages and B cells can all act as antigen-presenting cells (APC).
  • Dendritic cells are the most important APC because they are most efficient at taking up antigens and processing them for presentation to T cells. Tumor cells that express antiben bound to MHC class I can also be antigen-presenting cells. 
  • Antigen-presenting cells must present antigen in a membrane glycoprotein known as the Major Histocompatibility Complex (MHC).
  • MHC molecules are membrane proteins with extracellular domains that bind peptide fragments from proteins which were degraded inside the cell. MHC molecules bind to the peptide fragments before they reach the surface of the antigen-presenting cell.
  • There are two different classes of MHC molecules, which correspond to the two major types of T cells.
  • MHC class I molecules collect peptides derived from intracellular viral proteins degraded in the cytosol by the proteasome. They are expressed on various cell types, including many epithelial cells.
  • MHC class I molecules bind viral peptides and then are recognized by cytotoxic CD8+ T cells.
  • MHC class II molecules bind peptides derived from extracellular proteins that have been endocytosed and processed via the MHC class II machinery.

Used with permission from Macmillan Publishers Ltd: Nature Reviews Immunology12, 813-820, copyright 2012.

  • MHC class II molecules are expressed on classical antigen-presenting cells, such as dendritic cells and macrophages.
  • CD8 and CD4 co-receptors on T cells bind to MHC class I and MHC class II molecules, respectively.
  • Cytotoxic cells express the CD8 co-receptor that binds to MHC class I molecules.
  • Th1 and Th2 cells express the CD4 co-receptor that binds to MHC class II molecules.

Used with permission from Macmillan Publishers Ltd: Nature Reviews Genetics 7, 917-928, copyright 2006.

Cross-Presentation

  • Certain APCs can phagocytose and process extracellular antigens with MHC class I molecules and then present these antigen-MHC I complexes to CD8+ T cells. This process is known as cross-presentation, or cross-priming.
  • Cross-priming allows CD8+ T cells (which are normally activated by intracellular antigens) to be primed by extracellular antigens. This is an important part of the development of immunity against tumors since tumors are a source of extracellular antigens.

Fig13

Used with permission from Macmillan Publishers Ltd: Nature Reviews Microbiology 5, 491-504, copyright 2007.

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