Ag. processing.ppt
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Professional antigen presenting cells such as macrophages, dendritic cells, and B cells express MHC class II molecules. These cells uptake antigens through phagocytosis, pinocytosis, or receptor-mediated endocytosis. The antigens are then processed through two pathways: the MHC class I pathway processes endogenous antigens in the cytosol using the proteasome, while the MHC class II pathway processes exogenous antigens in lysosomes. The processed antigen peptides bind to MHC molecules, which are then presented on the cell surface to activate CD4+ or CD8+ T cells depending on the MHC molecule.
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- 1. ANTIGEN PROCESSING AND PRESENTATION Dr. Ahmed M. Salih
- 5. Professional APC Macrophages, dendritic cells, and B cells, which can express MHC class II molecules. Other cell type capable of expressing MHC class II molecules eg. Endothelial cells, EC Fibroblasts Activated T cell
- 6. 1. Binding and uptake of antigen depends on the physical state of the antigen and the cell type involved. 2. Antigen processing MHC class I processing pathway MHC class II processing pathway 3. Antigen presentation Antigen processing
- 7. 1 Binding and uptake of antigen exogenous antigens Bacteria, cells and soluble proteins processed by APC endogenous antigens Produced within the cells, Such as viral proteins or tumor proteins processed by host cell
- 9. Uptake antigen by immature DC Pinocytosis Liquid or small granule Receptor-mediated endocytosis effective selective saturated FCR, R Phagocytosis Large molecular or microbe
- 10. Phagocytosis Large solid or molecular complex, such as bacteria, fragment of cells, etc. Phagecyte (mf, granulocyte) Pinocytosis Receptor-mediated pinocytosis Endocytosis Low levels of particulate or soluble antigens exocytosis Uptake antigen by MPC
- 11. nonspecifically engulfed BCR-mediated Uptake antigen by B cells
- 12. 2 Antigen processing Degradation of externally- or internally- derived antigen into short peptide sequences Association of the peptide with MHC molecules
- 13. Two antigen-processing pathways MHC class I MHC class II Major antigen sources endogenous antigen exogenous antigen Processing machinery proteasome lysosomal enzymes Cell type where active all nucleated cells professional APCs Site of antigen- MHC binding endoplasmic reticulum lysosome and endosome MHC utilized MHC class I MHC class II Presents to CD8+ T cell (Tc) CD4+ T cells (Th)
- 14. MHC class I processing pathway
- 15. MHC class I processing pathway Antigenic protein - proteosome - peptide fragment released into cytosol - binds to TAP protein moves to endoplasmic reticulum(ER) Newly synthesized Class I a chain and b2 microglobulin - move to ER calnexin binds to a chain peptide fragment and b2m bind to a chain release of a chain from calnexin complex moves to Golgi apparatus glycosylation in Golgi apparatus secretory vesicle plasma membrane
- 21. proteasome LMP, low molecular weight polypeptide or large multifunctional protease Structure: 20S - 26S Function: Degradation of protein
- 23. 26S protease cmplex 20S proteasome twin 19S cops
- 24. TAP, transporter associated with antigen processing structure: TAP-1 and TAP-2 function: transports small peptides (8-13 aa) to the ER
- 26. MHC class II processing pathway
- 28. Antigenic protein - endosome/lysosome peptide fragment Newly synthesized class II molecules move to ER and associate with invariant chain protein molecule move to Golgi apparatus move to endosomes/lysosomes release of invariant chain from class II molecule class II binds antigenic peptide fragment transport to cell surface MHC class II processing pathway
- 29. Endosome & lysosome acidic protease & lysosome enzymes Function Degrade protein into peptide fragments (10-30 aa)
- 30. invariant chain, Ii Function Promote the formation of MHC II a b dimer Directs the movement of newly synthesized class II molecules into the Golgi and then the late endocytic compartment of the cell Prevent the binding of antigenic peptides to class II molecules, at least until the class II molecule reaches the late endocytic compartment
- 32. 3 Antigen presentation Antigen presentation The activation of T cells via T cell receptors, which specifically recognize antigenic peptide in association with either MHC class I or II molecules on the surface of APC.
- 34. Thank You