Binding of Epitopes from Endogenous Antigens to MHC- I Molecules in a Dendritic Cell

Endogenous antigens are those located within the cytosol of the cells of the body. Examples include:

a. Viral proteins produced during viral replication,
b. Proteins produced by intracellular bacteria such as Rickettsias and Chlamydias during their replication,
c. Proteins that have escaped into the cytosol from the phagosome of phagocytes such as antigen-presenting dendritic cells,
d. Tumor antigens produced by cancer cells, and
e. Self peptides from human cell proteins.

One of the body's major defenses against viruses, intracellular bacteria, and cancers is the destruction of infected cells and tumor cells by cytotoxic T-lymphocytes or CTLs. These CTLs are effector cells derived from naive T8-lymphocytes during cell-mediated immunity. However, in order to become CTLs, naive T8-lymphocytes must become activated by cytokines produced by antigen-presenting dendritic cells. This interaction between dendritic cells and naive T8-lymphocytes occurs primarily in the lymph nodes, the lymph nodules, and the spleen. The process can be summarized as follows:

1. In addition to microbes, dendritic cells and macrophages also engulf and degrade infected cells, tumor cells, and the remains of killed infected and tumor cells. It is thought that in this manner, endogenous antigens from other cells are able to enter the dendritic cell. During phagocytosis, some protein antigens from the engulfed exogenous antigens are translocated from the phagosomes or phagolysosome of the dendritic cell to the cytosol wher they become "endogenous" antigens.
2. These cytosolic protein antigens then pass through proteasomes, where proteases and peptidases chop the protein up into a series of peptides.
3. A transporter protein called TAP located in the membrane of the cell's endoplasmic reticulum then transports these peptide epitopes into the endoplasmic reticulum where they bind to the grooves of various newly made MHC-I molecules.
4. The MHC-I molecules with bound peptides are then transported to the Golgi complex and placed in exocytic vesicles.
5. The exocytic vesicles carry the MHC-I/peptide complexes to the cytoplasmic membrane of the cell where they become anchored to its surface.

The MHC-I molecules with bound peptide on the surface of the APCs can now be recognized by naive T8-lymphocytes possessing TCRs and CD8 molecules with a complementary shape. This recognition of the peptide epitope by the TCR serves as a first signal for activating the naive T8-lymphocyte for cell-mediated immunity function.

(Through the process of cross-presentation, some antigen-presenting dendritic cells can cross-present epitopes of exogenous antigens to MHC-I molecules for eventual presentation to naive T8-lymphocytes.)

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