Fortress body III_ Antigen processing and presentation_ part 2 .pdf

11/11/23 Fortress body III: Antigen processing and presentation: part 2 Antigen presenting pathways: Endogenous: presenting on class i Processes proteins and presents them to CD8+ T cells. Exogenous: presenting das on 11 Processes proteins captured from outside to the CD4+ T cells. Endogenous Pathwa...

11/11/23 Fortress body III: Antigen processing and presentation: part 2 Antigen presenting pathways: Endogenous: presenting on class i Processes proteins and presents them to CD8+ T cells. Exogenous: presenting das on 11 Processes proteins captured from outside to the CD4+ T cells. Endogenous Pathway: very long needs to be shortened 1. The virus infects the cell and will express its proteins in the cytosol. The blue squiggle is the protein and in red is the antigenic peptide ( short run of amino acids ). The viral protein is endogenous because it is being expressed inside the cell. 2. The proteasome is a multi catalytic protease. The protein is fed through the proteasome, so the protein is degraded and out of the other end comes the epitope. 3. The epitope needs to enter the endoplasmic reticulum to come into contact and associate with the MHC class I. It does this via a transporter associated with antigen presentation created by TAP1 and TAP2 making it a heterodimeric protein. 4. The process of getting the MHC class I ready involves many different proteins: calnexin, ERp57, calreticulin and tapasin ( coded for by TAPBP, which is on the MHC gene locus ). These are all involved in making sure that MHC class I folds correctly and brings it along to the TAP complex. 5. Once the epitope has been loaded on, the MHC moves to the cell surface to present it to the T cell. Exogenous Pathway: This involves the capture a degradation of an antigen and then loads it onto MHC class II. 1. The antigen is captured and ends up in a lysosome via a number of processes. There is a reduction of pH in the lysosome. Proteases breakdown the protein and leave the antigenic peptide. 2. MHC class II undergoes the normal process, but somehow it’s got to interact with or intercept the vesicle that contains the antigenic peptide. It will go through the endoplasmic reticulum alongside MHC class I. But instead of binding peptide and going to the cell surface. It gets directed to the vesicle containing the antigenic peptide. In order to protect it from binding to anything other than the peptide, an invariant chain is added to cover the region of the MHC, that would usually bind to the antigenic peptide. 3. Now it’s bound to the vesicle ( now called the MIIC vesicle ) you’ve only got a little bit of the invariant chain left, but it is still covering the binding site. So a HLA DM protein degrade it and allows the epitope to bind. 4. The complex moves to the cell surface to present it to the T cell. Peptides ( antigen ) bound in MHC class I and II are different: Peptide binding pockets are a de ned size in MHC class I, whereas they’re more open at the ends in class II. Peptides are generally longer in class II than class I.