Lecture notes
antigen processing and presentation
- Module
- Mechanisms of pathology
- Institution
- Aston University, Birmingham (Aston)
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Antigen processing and presentation.T cells recognise processed and presented antigens
• Protein antigen in cell.
• Antigen processing by breakdown of protein.
• Presentation of peptide by MHC molecule.
• The processing of a protein from a pathogen into a peptide that’s presented on the
MHC.
• The peptides are taken up into the cells or they are expressed onto the cells in the
case of a viral infection, those antigens are then processed, and the protein is broken
down into small peptides and those peptides are loaded onto the MHC molecule
which is then shuttled to the cell surface for presentation by T cells.
• This is a critical process because T cells will only recognize antigen that has been
processed and is presented in the context of MHC.
Two classes of MHC.
• Similar structures based on Ig domains
• Folding forms a groove into which peptides bind
• MHC class I is composed of a single MHC chain
• MHC class II is composed of two MHC chains
• 2 classes of MHC that are parallel pathways that present peptides from different
types of pathogens.
• MHC class 1 and class 2 molecules have a similar structure. With a peptide binding
groove on the distal end and a transmembrane domain that anchors the molecule to
the cell membrane.
• MHC class 1 has one cell membrane domain and its structure is stabilized by a
constant protein called the beta 2 microglobulin.
• Whereas the MHC class 2 molecule is made out of 2 protein chains so alpha and beta
each of them with their own transmembrane domain, with that peptide binding
groove where the alpha and beta chains meet.
• Whereas in MHC class 1 the peptide binding groove is only dictated by the alpha
chains.
• MHC class 1 is a single MHC chain with one transmembrane domain
• MHC class 2 has 2 transmembrane domains and 2 chains.
Two classes of MHC for two major classes of T cells.
• MHC class 2 + peptide (Ag). Primarily expressed on APCs. Extracellular pathogens.
Activate CD4 T cell responses.
• MHC class 1 + peptide (Ag). Expressed by almost all cells. Intracellular pathogens.
Activate CD8 T cell responses.
• 2 major classes of T cells and their interaction with T cells is important in how they
mediate their function.
• T helper cells like to tell other cells what to do.
• They only interact with MHC class 2.
• Therefore, they only interact with antigen presenting cells.
• These cells recognize extracellular pathogens like bacteria and fungi and when they
are actuvated these helper T cell responses turn on the activity of a number of other
, immune cells to generate the type of immune cell that is needed to eradicate that
type of pathogen.
• Cytotoxic t cells are CD8 positive.
• And they only interact with MHC class 1.
• MHC class 1 is expressed by nearly all of our cells.
• This presents intracellular pathogens. This is essentially viral derived peptides.
• When a cytotoxic T cell recognizes its peptide in MHC class 1, it then responds by
inducing apoptosis and killing that cell because it reads that as being a virus infected
cell that needs to die.
Exogenous pathway and endogenous pathway.
• Both the pathways end up with peptide presented in class 1 or 2 on the surface.
• Followed by the interaction of the appropriate T cell.
• How this peptide gets onto MHC is different for the two peptide pathways.
• Endogenous pathway:
• That loads peptides onto MHC class 1, these antigens are coming from the cytosol of
the cell.
• They are ubiquinated and processed through the proteasome and loaded into the
endoplasmic reticulum through TAP.
• And then those peptides can bind onto MHC class 1 as it is being processed through
the endoplasmic reticulum.
• And it is then shuttled to the cell surface.
• Exogenous pathway:
• MHC class 2 pathway, there is two different sets of vesicles that merge together in
order for this peptide binding to happen.
• MHC class 2 molecule moving through the endoplasmic reticulum has its binding
groove protected by the invariant chain.
• The exogenous antigen is taken up from outside the cell into phagolysosome and
then we can get binding of the peptide to MHC class 2, when those two vesicles
merge.
• And then the MHC can be shuttled to the cell surface.
• And be ready for antigen presentation.
• Cytotoxic T cells interact with MHC class 1 (HLA class 1 in humans) and that allows
the cytotoxic T cells to kill viral infected T cells.
• Helper T cells only interact with MHC class 2, which is only expressed on antigen
presenting cells.
• And these T cells once they have found their cognate antigen on MHC class 2 they
can then differentiate down a number of different pathways that are specifically
designed to fight off particular pathogens.
MHC expression reflects T cell effector functions.
• CD8 T cells interact with MHC class 1.
• And cell contact in which the CD8 positive T cell reads the cell as being infected with
a virus leads to a dead virus infected cell.
• And that cell is killed through apoptosis.
• With CD4 positive T cells:
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