Antigen Processing and Presentation Flashcards
What is antigen presentation?
The displaying of peptides derived from pathogens or other proteins on the dendritic cell surface in a way that T cells can see.
What provides the physical structure to display antigenic peptides to the T cells?
MHC proteins (major histocompatibility complex proteins) expressed on the cell surface
What are the two main types of MHC proteins?
MHC class I and MHC class II.
Both proteins have grooves that can bind peptides.
Describe the structure of MHC Class I Proteins.
- are expressed on all nucleated cells,
- consist of transmembrane α chain that is non-covalently associated with a soluble protein called β2-microglobulin,
- the peptide-binding groove is located within the α chain,
- a peptide (approximately 8 – 12 amino acids in length) binds to the nascent MHC class I protein (the ends of the peptide interact with the MHC class I protein).
Describe the structure of MCH Class II proteins.
- expressed only on antigen-presenting cells such as dendritic cells, B cells, macrophages and thymic epithelial cells (these cells also express MHC class I proteins).
- consist of two non-identical transmembrane polypeptide chains (called the α and β chains),
- the peptide-binding groove is formed between the α and β chains,
- a peptide of at least 13 amino acids in length binds to the MHC class II protein (the ends of the peptide do not interact with the MHC class II protein).
What does antigen processing and presentation refer to?
The degradation of protein into peptide fragments (antigen processing), and the binding and display of the antigen as a peptide fragment bound to MHC proteins on the surface of a cell (antigen presentation).
Where are the peptides displayed by MHC class I proteins derived from?
Proteins that are in the cytoplasm of a cell
(normally intracellular proteins in healthy uninfected cells and viral proteins in virus-infected cells – in both cases, the proteins are synthesized by the ribosomes in the cytoplasm of the cell).
Where are the peptides displayed by MHC class II proteins derived from?
Soluble proteins that are taken up by a cell via endocytosis or phagocytosis into an endosome or phagosome.
The proteins can include normal blood proteins, toxins, bacteria or virus particles.
How many pathways exist for processing and presentation of protein into peptide fragments?
There are two main pathways for processing and presentation of protein into peptide fragments: the endogenous pathway and the exogenous pathway.
A third pathway, known as the cross-presentation pathway, contains elements of both the endogenous and exogenous pathways.
Describe The Endogenous Protein Processing Pathway and MHC Class I Peptide Loading.
- the intracellular proteins are degraded into peptides by the proteasome
- transporter proteins called TAP proteins move the resulting peptides from the cytoplasm into the lumen of the endoplasmic reticulum (ER),
- a peptide binds to the nascent MHC class I protein,
- the MHC class I-peptide complexes are then transported to the cell surface.
What is the proteasome and where is it located?
a protease complex located in the cytoplasm
Describe The Exogenous Protein Processing Pathway and MHC Class II Peptide Loading.
- MHC class II proteins with associated invariant chain (Ii) proteins leave the ER in vesicles,
- after endo- or phagocytosis of the bacterium/virus/protein the endo- or phagosome fuses with lysosomes that contain lysozyme, proteases and bactericidal substances,
- proteases degrade the proteins (bacterial, virus or blood) into peptides,
- peptides derived from these proteins usually remain inside the vesicles (they do not enter the cell’s cytoplasm),
- the vesicles containing the MHC class II/Invariant complexes fuses with the vesicles containing peptide fragments in the MIIC region of the cell,
- the invariant chain is degraded to a smaller fragment called CLIP which occupies the peptide-binding site,
- CLIP is replaced with a peptide fragment,
- the MHC class II-peptide complexes are then transported to the cell surface.
Describe Cross-presentation Pathway for Presentation of Peptides Derived From Exogenous Proteins on MHC Class I Proteins.
Cross-presentation is a special case where MHC class I proteins display peptides derived from exogenous proteins.
Dendritic cells are capable of cross-presentation; this is important in the immune responses to virus pathogens.
One model of cross-presentation suggests that peptides are derived from antigens (e.g., a virus particle) taken up by the cell in an endosome or a phagosome, and the contents of this vesicle are diverted to the proteasome.
From there, the processing of peptides follows the endogenous pathway.
Because of cross-presentation, the dendritic cell can present peptides derived from exogenous antigens on both MHC class I proteins and MHC class II class proteins.
How can the dendritic cell present peptides derived from exogenous antigens on both MHC class I proteins and MHC class II proteins?
Cross-presentation
How is the cell able to communicate to T cells that it has become infected with a virus?
In eukaryotic cells, the number of copies of a particular protein in a cell is carefully regulated. Every protein is subject to continuous turnover. In other words, “old” copies of the protein are broken down into their constituent amino acids and “new” copies of the protein are made.
This turnover of proteins also includes the MHC proteins. The turnover of MHC proteins means that, if a cell becomes infected with a virus, it replaces “old” MHC proteins displaying self-peptides with “new” MHC proteins that display peptides derived from viral proteins.
What is a polygenic gene?
There are several genes that encode proteins of a similar function (eg; MHC genes)
How many types of MHC class I proteins do humans have?
Three types of MHC class I proteins: HLA-A, HLA-B, and HLA-C.
HLA is the acronym for “human leukocyte antigen.”
All three types of MHC class I proteins are expressed on all nucleated cells.
How many types of MHC class II proteins do humans have?
Three types of MHC class II proteins: HLA-DP, HLA-DQ, and HLA-DR.
All three types of MHC class II proteins are expressed on macrophages, dendritic cells, B cells and thymic epithelial cells (these are all antigen presenting cells).
