Antigen Presentation Flashcards
What is an antigen?
Structural protein of a pathogen e.g. cell surface protein
What is the First Law of Immunology?
Lymphocytes detect antigen by various means:
B-cell receptor detects whole antigen on the surface of the pathogen
T-cell receptor detects digested antigen fragments (peptides) displayed on the surface of other cells
What is MHC?
Major Histocompatability complex which is responsible for predenting antigenic peptides for T-cells via the immunological synapse (MHC to TCR information release)
Describe the structure of MHC Class I an II
Class I: 3 Alpha subunits - Alpha 1 and 2 binding produces the specific antigen binding domain
Class II: 2 Alpha subunits and 2 Beta Subunits - Alpha 1 and Beta 1 contribute to the antigen binding domain
Both MHC Classes are embedded within the lipid bilayer
How is the Peptide binding groove specific to certain antigen?
Peptide binding groove contains anchor residues which will only bind certain amino acids - amino acids have to be the same or similar amino acids and in the same place on the antigen in order for the antigen to anchor to the MHC. Any peptide with a similar binding motif will attach.
Where do the different MHC classes reside? ICF or ECF
What is the Second Law of Immunology?
MHC Class I molecules present peptides from antigen located in the cytoplasm (pathogen in intracellular fluid)
MHC Class II molecules present pepties from antigen located in the tissue fluid (pathogen in extracellular fluid)
What is the MHC Class I pathway?
Detects intracellular antigen such as viral proteins:
1. Proteasome (the cells protein recylcer and degrader) also breaks down viral proteins found in the cytoplasm
2. Peptides are then transported from the cytoplasm to the endoplasmic reticulum by TAP transporters (MHC Class I in the ER)
3. If the viral peptide has the correct motif it will bind to MHC
4. If MHC binds viral peptide MHC peptide complex is formed and are transported to the cell surface through the golgi to present antigen for lymphocytes
5. Recognised by CD8 T-cell
How is the MHC Class II produce in the ER when MHC Class I is working in the ER?
Detects extracellular antigen most commonly bacterial:
MHC Class II is only expressed by specalist antigen presenting cells (APCs) - Macrophages, B-cells, dendritic cells
1. When MHC Class II are synthesised in the ER they have an invariant chain chaperone protein which blocks binding so MHC Class I only works in ER
2. MHC Class II leaves ER and enters the secretory pathway
How does MHC Class II present antigen?
- Cell uptakes antigen (various different ways e.g. phagocytosis, pinocytosis etc.)
- Antigens are endocytosed and digested into peptides by the acion of lysosomal acid proteases
- The endocytotic (antigen) and secretory MHC Class II merge to form MIIC Compartment
- The invariant chain is degraded, leaving behind a CLIP peptide in the peptide binding groove
- If an antigen that has higher affinity than the CLIP peptide comes into contact with this MHC they bind
- MHC:Peptide complex presented to on surface to CD4 T-cells
Describe the different APCs
Expression of both MHC Classes:
- Dendritic cells present to naive T-cells in lymphatic tissues to stimulate proliferation and differentiation
- Macrophages and B-cells present to mature CD4 T-helper clls
What is the Dendritic Cell patway to presenting antigen?
- Immature dendritic cells are located in the epithelial surfaces where they engulf antigen
- They migrate via afferent lymphatics to the lymph node during ehich time they process antigen
- They take up residency within the lymph node paracortex where they will present antigen to naive t-cells
What are the problems with MHC?
Individual MHC molecule can only present a limited set of peptides but, there are a lot of different pathogens with diverse antigens and the capacity to mutate
