Binding of Peptide Epitopes from Exogenous Antigens to MHC-II Molecules by a B-Lymphocyte

Exogenous antigens are those from outside cells of the body. Examples include bacteria, free viruses, yeasts, protozoa, microbial proteins and polysaccharides, and toxins. These exogenous antigens bind to B-cell receptors either directly, or, more commonly, from the surface of either specialized macrophages or follicular dendritic cells (FDCs) located in the lymph nodes and the spleen. The antigens then enter B-lymphocytes through endocytosis. After lysosomes fuse with the phagosome, protein antigens are degraded by proteases into a series of peptides. These peptides eventually bind to grooves in MHC-II molecules and are transported to the surface of the B-lymphocyte. Effector T4-lymphocytes are then able to recognize peptide/MHC-II complexes by means of their T-cell receptors (TCRs) and CD4 molecules.

1. Epitopes of exogenous antigens, such as viruses, bind to a complementary shaped B-cell receptor on a B-lymphocyte. The antigen is engulfed and placed in a phagosome.
2. Lysosomes fuse with the phagosome forming an phagolysosome.
3. Protein antigens are degraded into a series of peptides.

4. MHC-II molecules are synthesized in the endoplasmic reticulum and transported to the Golgi complex. Once assembled, within the endoplasmic reticulum, a protein called the invarient chain (Ii) attaches to the the peptide-binding groove of the MHC-II molecules and in this way prevents peptides designated for binding to MHC-I molecules within the ER from attaching to the MHC-II.
5. As the MHC-II molecules with bound Ii chain are transported to the Golgi complex, the Ii is cleaved, leaving a short peptide called CLIP in the groove of the MHC molecule.
6&7. The vesicles containing the MHC-II molecules fuse with the peptide-containing phagolysosomes. The CLIP peptide is removed from the MHC=II molecules and the peptide epitopes are now free to bind to the grooves of the MHC-II molecules.
8. The MHC-II molecules with bound peptides are transported to the cytoplasmic membrane where they become anchored. Here, the peptide and MHC-II complexes can be recognized by effector T4-lymphocytes by way of TCRs and CD4 molecules having a complementary shape.

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