Antigen Processing and Presentation (University of Portsmouth)

Antigen Processing and Presentation Learning Objectives On completion of this session you should be able to 1) Comprehend the different pathways of antigen processing and presentation by MHC class I and II molecules. 2) Identify key molecular components involved. Antigen Processing and Pr...

Antigen Processing and Presentation Learning Objectives On completion of this session you should be able to 1) Comprehend the different pathways of antigen processing and presentation by MHC class I and II molecules. 2) Identify key molecular components involved. Antigen Processing and Presentation 1) Antigen processing - the generation and binding of peptides to MHC molecules 2) Antigen presentation - displaying peptides on the cell surface in association with MHC molecules 3) MHC Class I and II molecules bind peptides derived from different cellular locations: Class I – cytosolic Class II – vesicular Antigen Processing and Presentation Antigen Processing and Presentation The Processing “Machinery” 1. Proteosome - Large, multicatalytic protease complex ~28 subunits Degrades cytosolic proteins 2. TAP Transporter - transporter associated with antigen processing Heterodimer of TAP-1 and TAP-2 proteins (encoded by MHC) Transports peptides across the endoplasmic reticulum (ER) Antigen Processing and Presentation 3. Calnexin - ER membrane-bound protein (88 kDa) Retains MHC class I molecules in ER until peptide is bound Chaperone protein 4. PLC (Peptide Loading Complex) Comprises chaperone proteins: a) calreticulin – similar function to calnexin b) tapasin – links MHC Class I to TAP c) ERp57 – mediates peptide binding to Class I Antigen Processing and Presentation 5. Endoplasmic Reticulum Aminopeptidase associated with Antigen Processing (ERAAP) Trims peptides to correct length 6. Invariant Chain (Ii, CD74) - MHC Class II associated Invariant chain Associates with newly formed MHC class II molecules to prevent peptide binding in ER Targets delivery of new Class II molecules to low pH endosomes Antigen Processing and Presentation with Class I Antigen Processing and Presentation with Class II Summary 1. Antigen processing involves two main pathways corresponding to MHC class I and II molecules. 2. The endogenous pathway, associated with MHC class I, processes intracellular antigens. Proteins are degraded by the proteasome into peptides, which are then transported into the endoplasmic reticulum by the transporter associated with antigen processing (TAP), where they bind to MHC class I molecules and are presented on the cell surface to CD8+ T cells. 3. The exogenous pathway, linked to MHC class II, processes extracellular antigens. These antigens are taken up into endosomes/lysosomes, where they are degraded into peptides. These peptides bind to MHC class II molecules, which are then transported to the cell surface to present antigens to CD4+ T cells. 4. Key molecular components in these pathways include the proteasome, TAP, and the endosomal/lysosomal system, all of which are crucial for the correct processing and presentation of antigens to the immune system.