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Endogenous and exogenous pathway
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Allow proper understanding on endogenous and exogenous pathway of antigen presenting cells with MHC with suitable diagram and enzymes
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DAV University, Department of BiochemistryAntigen processing and
presentation with MHC
Immunology
Dr. Jasweer Kaur
20
, Most Cells Can Present Antigen with Class I MHC; Presentation with Class II
MHC Is Restricted to APCs
Since all cells expressing either class I or class II MHC molecules can present peptides to
T cells, strictly speaking they all could be designated as antigen-presenting cells. However, by
convention, cells that display peptides associated with class I MHC molecules to CD8+ TC cells
are referred to as target cells; cells that display peptides associated with class II MHC molecules
to CD4+ TH cells are called antigen-presenting cells (APCs). A variety of cells can function as
antigen-presenting cells. Three cell types are classified as professional antigen-presenting cells:
dendritic cells, macrophages, and B lymphocytes. Because nearly all nucleated cells express
class I MHC molecules, virtually any nucleated cell is able to function as a target cell presenting
endogenous antigens to TC cells. Most often, target cells are cells that have been infected by a
virus or some other intracellular microorganism. However, altered self-cells such as cancer cells,
aging body cells, or allogeneic cells from a graft can also serve as targets.
Two Processing and Presentation Pathways
The immune system uses two different pathways to eliminate intracellular and
extracellular antigens. Endogenous antigens (those generated within the cell) are processed in the
cytosolic pathway and presented on the membrane with class I MHC molecules; exogenous
antigens (those taken up by endocytosis) are processed in the endocytic pathway and presented
on the membrane with class II MHC molecules (Figure 1).
Endogenous Antigens: The Cytosolic Pathway
The pathway by which endogenous antigens are degraded for presentation with class I MHC
molecules utilizes the same pathways involved in the normal turnover of intracellular proteins.
1. Peptides for Presentation Are Generated by Protease Complexes Called
Proteasomes
Intracellular proteins are degraded into short peptides by a cytosolic proteolytic system
present in all cells. Those proteins targeted for proteolysis often have a small protein, called
ubiquitin, attached to them . Ubiquitin-protein conjugates can be degraded by a multifunctional
protease complex called a proteasome. A proteasome can cleave peptide bonds between 2 or 3
different amino acid combinations in an ATP-dependent process.
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