Exam II Flashcards
what is antigen processing?
series of intracellular events in which antigen presenting cells make antigen available for T cells
Antigen processing involves
- Uptake of antigens (proteins)
- Degradation to peptides of MHC I or II
- Transport to the cell surface
what is antigen presentation?
Presentation of MHC peptide complexes on the cell surface for the stimulation of T cells
Typically done by antigen presnting cells (APC)
1. Dendritic cells
2. macrophages
3. B cells
Types of APC?
Dendritic Cells
Macrophages
B cells
T cell receptor binds to both
peptide and MHC molecule
T cells must have
MHC in order to be able to respond to an antigen
Cytotoxic T cells
CD8
CD8 complex consists of
alpha and beta
Helper T cell
CD4
CD8 T cell, their T cell receptor binds to
alpha3 domain of MHC class I
CD4 T Cell, their T cell receptor binds
Beta2 domain of MHC class II
Endocytic processing pathway
Exogenous (antigens from outside the cell) or MHC Class II processing pathway
Bound to MHC Class II and taken into the cell
Cytosolic
Endogenous (proteins that exist in the cytoplasm) or MHC Class I processing pathway
Endocytic Pathway
- Antigen is taken up from the extracellular space into intracellular vesicles
- In early endosomes of neutral pH, endosomal proteases are inactive
- Acidification of vesicles activates proteases to degrade antigen into peptide fragments
- Vesicles containing peptides fuse with vesicles containing MHC Class II molecules
The MCH class II binds to the peptide.
lower pH, more degradation
MHC II molecule is synthesized in
lumen of ER
How MHC class II gets to the processed peptides
- Invariant chains blocks binding of peptides to MHC class II molecules in the ER
- In vesicles, invariant chain is cleaved, leaving the CLIP fragment bound
- CLIP blocks binding of peptides to MHC Class II in vesicles
- HLA-DM facilitates release of CLIP, allowing peptides to bind
MHC Class II - endocytic
presents peptide antigens
Invariant chain - endocytic
directs class II away from secretory pathway to endocytic pathway and blocks peptide loading in the ER
HLA-DM -endocytic
acts as a chaperone or catalyst to facilitate exchange of CLIP with antigenic peptides
pH - endocytic
low pH and degradative environment facilitates denaturation of antigenic proteins
proteases - endocytic
cathepsins and other degradative enzymes chew up antigens into peptides
Cytoplasmic pathway (antigens are in the cytoplasm)
proteasome - degrades the antigen protein into peptides,
- class I is heavy chain is stabilized by calnexin until B2-microglobulin binds
- Calnexin is released and the heterodimer of class I heavy chain and b2m forms the peptife loading complex with calreticulin, tapasin, TAP, ERp57, PDI
- A peptide delivered by TAP binds to the class I heavy chain, forming the mature MHC class I molecule
TAP (I and II)- transport port through the ER membrane.
- The class I molecule dissociates from the peptide loading complex and is exported from the endoplasmic reticulum
MHC class I protein
alpha chain (3 domains) - transmembrane protein
beta 2 microglobulin - associated with all MHC 1 - stabilizes it.
peptides that are produced in the cytosol are transported into the ER
Peptides re generated in the cytoplasm and then transported through TAP into the ER and associate with MHC class I