Antigen Processing and Presentation Pathways
The immune system typically uses different pathways to eliminate intracellular and
extracellular antigens. As a general rule, endogenous antigens (those generated within the
cell) are processed in the cytosolic or endogenous pathway and presented on the
membrane with class I MHC molecules. Exogenous antigens (those taken up from the
extracellular environment by endocytosis) are typically processed in the exogenous
pathway and presented on the membrane with class II MHC molecules.
Experiments carried out by L. A. Morrison and T. J. Braciale provided an excellent
demonstration that the antigenic peptides presented by class I and class II MHC molecules
follow different routes during antigen processing. Examining the T-cell responses, they
derived the following general principles about the two pathways:
• Class I presentation requires internal synthesis of virus protein, as shown by the
requirement that the target cell be infected by live virus, and by the inhibition of
class I presentation observed when protein synthesis was blocked by the inhibitor
emetine.
• Class II presentation can occur with either live or replication incompetent virus;
protein synthesis inhibitors had no effect, indicating that new protein synthesis is not
a necessary condition of class II presentation.
• Class II, but not class I, presentation is inhibited by treatment of the cells with an
agent that blocks endocytic processing within the cell (e.g., chloroquine).
Endogenous Pathway
In eukaryotic cells, protein levels are carefully regulated. Every protein is subject to
continuous turnover and is degraded at a rate that is generally expressed in terms of its
half-life. Defective ribosomal products are polypeptides that are synthesized with
imperfections and constitute a large part of the products that are rapidly degraded to their
constituent amino acids and recycled, but some persist in the cytosol as peptides. The cell
samples these peptides and presents some on the plasma membrane in association with
class I MHC molecules, where cells of the immune system can sample these peptides to
survey for foreign proteins. The pathway by which these endogenous peptides are
generated for presentation with class I MHC molecules utilizes mechanisms similar to those
involved in the normal turnover of intracellular proteins.
Endogenous Pathway is concerned with the MHC class I molecules associated with
endogenous antigens. The process begins with the ubiquitination of the endogenous
antigens, which marks them for degradation by the proteasomes. This distinct proteasome,
called the immunoproteasome. The proteasomes break these antigenic proteins into small
peptides approximately 8-9 amino acids long; these are, in turn, transported with the
Transporter associated with Antigen Processing (TAP) complex into the endoplasmic
The immune system typically uses different pathways to eliminate intracellular and
extracellular antigens. As a general rule, endogenous antigens (those generated within the
cell) are processed in the cytosolic or endogenous pathway and presented on the
membrane with class I MHC molecules. Exogenous antigens (those taken up from the
extracellular environment by endocytosis) are typically processed in the exogenous
pathway and presented on the membrane with class II MHC molecules.
Experiments carried out by L. A. Morrison and T. J. Braciale provided an excellent
demonstration that the antigenic peptides presented by class I and class II MHC molecules
follow different routes during antigen processing. Examining the T-cell responses, they
derived the following general principles about the two pathways:
• Class I presentation requires internal synthesis of virus protein, as shown by the
requirement that the target cell be infected by live virus, and by the inhibition of
class I presentation observed when protein synthesis was blocked by the inhibitor
emetine.
• Class II presentation can occur with either live or replication incompetent virus;
protein synthesis inhibitors had no effect, indicating that new protein synthesis is not
a necessary condition of class II presentation.
• Class II, but not class I, presentation is inhibited by treatment of the cells with an
agent that blocks endocytic processing within the cell (e.g., chloroquine).
Endogenous Pathway
In eukaryotic cells, protein levels are carefully regulated. Every protein is subject to
continuous turnover and is degraded at a rate that is generally expressed in terms of its
half-life. Defective ribosomal products are polypeptides that are synthesized with
imperfections and constitute a large part of the products that are rapidly degraded to their
constituent amino acids and recycled, but some persist in the cytosol as peptides. The cell
samples these peptides and presents some on the plasma membrane in association with
class I MHC molecules, where cells of the immune system can sample these peptides to
survey for foreign proteins. The pathway by which these endogenous peptides are
generated for presentation with class I MHC molecules utilizes mechanisms similar to those
involved in the normal turnover of intracellular proteins.
Endogenous Pathway is concerned with the MHC class I molecules associated with
endogenous antigens. The process begins with the ubiquitination of the endogenous
antigens, which marks them for degradation by the proteasomes. This distinct proteasome,
called the immunoproteasome. The proteasomes break these antigenic proteins into small
peptides approximately 8-9 amino acids long; these are, in turn, transported with the
Transporter associated with Antigen Processing (TAP) complex into the endoplasmic
