Antigen processing and Presentation Flashcards
BCR recognizes
and binds free antigen that is part of a larger pathogen or toxin
TCR recognizes
and binds both antigenic peptide and MHC to which peptide is bound
- Protein antigens must be processed into peptide fragments and presented by self-MHC molecules in order to be recognized by TCRs on responding T cells
Endogenous antigens
are processed via the cytolytic or endogenous pathway and presented on MHC class 1
Exogenous antigens
are processed via the exogenous pathway and presented on MHC class 2 molecules
Class 1 presentation
requires cytosolic or endogenous processing
Class 2 presentation
requires exogenous processing
MHC class 1 molecules interact with peptides derived from
cytosolic degradation of endogenously synthesized proteins
- cytosol
MHC class 2 molecules associate with peptides derived from
Endocytic degradation of exogenous antigen
- Endosome/Lysosome
The amount or level of each type of protein inside a cell is carefully regulated primarily through?
- Degrade proteins (proteasome, lysosomes)
2. Translation/ transcription (make more)
Peptides that associate with MHC class 1 molecules
are generated by protease complexes called proteasome
Proteasome
- recognizes and degrades Ubiquitin tagged proteins
- protease complexes that generate peptides that associate with MHC class 1 molecules
Ubiquitin
used to ‘tag’ intracellular proteins for degradation
immunoproteasome
cleaves ubiquitinated proteins into fragments that pair better with MHC molecules
Endogenous pathway
- Peptides are transported from the cytosol to the Rough endoplasmic reticulum (RER)
- TAP molecules in the RER move the fragments
- MHC class 1 molecules synthesized by ribosomes on the RER anchor in the RER membrane after they translation
- Chaperone proteins help fold MHC class 1 and put it in close proximity to TAP
- ERAP trims long peptides to a suitable size for MHC class 1 grooves
- Endogenous antigen is degraded by an immunoproteasome
- Peptide is transported to RER via TAP
- MHC class 1 alpha chain binds calnexin and ERp57, the beta2-microglobulin. Calnexin dissociates. Calreticulin and tapas in bind. MHC captures peptide, chaperones dissociate
- MHC class 1- peptide is transported from RER to golden complex to plasma membrane
Chaperone proteins
- Calnexin
- ERp57
- Calreticulin
- Tapasin
- Help fold MHC class 1 and put it close proximity to TAP
ER aminopeptidase (ERAP)
trims long peptides to a suitable size for MHC class 1 grooves
Extracellular material can gain access to vehicular components through
- Phagocytosis
- Receptor-mediated endocytosis
- Autophagy
Phagocytosis
actin mediate
Receptor-mediated endocytosis
- receptor will be recycled
- pH drop
- antigen will be shuttled to lysosome
- how B-cells recycles
Autophagy
will be directed toward the lysosome
Peptides that associate with MHC class 2 molecules are generated from extracellular antigens in
membrane- bound vesicles
- endosomes
Endosomes
are fused with lysosome as an MHC late lysosome which becomes acidic and helps degrade contents
Exogenous pathway
- MHC class 2 molecules are produces, associated with invariant chain (Ii) and exported in nestles from ER to Golgi
- Peptides assemble with class 2 MHC molecules in late endosomes
- The invariant chain (Ii) binds to MHC class 2 alpha and beta chains, blocking endogenous peptides from bindind
- MHC-Ii complex is routed through Golgi to endocytic pathway compartments
- Invariant chain is degraded, leaving CLIP fragment
- Exogenous antigen is taken up, degraded, routed to endocytic pathway compartments
- HLA-DM mediates exchange of CLIP for antigenic peptide
- MHC class 2-peptide is transported to palms membrane
Invariant chain
- prevents peptide from binding to the groove too early in ER
- uses sorting signals to direct MHC class 2 molecule-containing vesicles to peptide-containing endocytic compartments
CLIP
Ii is initially degraded by proteolytic activity within endocytic compartment to class 2-associated invariant chain
HLA-DM
exchanges CLIP out of the groove for a peptide
How does the immune system activate CD8+ T cells to eliminate intracellular microbes if the APC isn’t infected?
dendritic cells are capable of carrying out cross-presentation
Cross-presentation
- exogenous antigens are redirected to the endogenous presentation pathway
- This allows for antigen presentation on MHC class 1 molecules
