BIOL 435 Ch. 7 p.2 (MHC and Ag Presentation) Flashcards
immune responsiveness
-different capability of MHC II alleles to present Ag may dictate overall strength of immune response between individuals
2 reasons for variability in immune responsiveness
- Determinant-selection model
- Holes-in-the-repertoire model
* both appear to be correct
determinant selection model
-MHC class 2 molecules differ in ability to bind particular processed Ag peptides
holes-in-the-repertoire model
-T cells with TCRs that recognize foreign Ags closely resembling self-Ags may be eliminated during thymic development
Ag processing and presentation pathways
- Cytosolic or endogenous processing: Class I
2. Exogenous processing: Class II
endogenous pathway general
- Proteasomes process peptides
- Peptides transported from cytosol to RER
- TAP
proteasomes
- protease complexes where peptides are generated
- tagged proteins are feed into them
1. Constitutive: common
2. Immuno
ubiquitin proteins
-used to ‘tag’ intracellular proteins for constitutive degradation
immunoproteasome
- subtle variant
- cleaves ubiquitinate proteins into fragments that pair better with MHC molecules
TAP
- transporter associated with Ag processing
- in RER membrane
- move the peptide fragments
MHC I from ribosomes on RER
-anchor in RER membrane after translation
chaperones
- aid peptide/MHC class I assembly
- Calnexin, ERp57, calreticulin and tapasin
- ER aminopeptidase (ERAP1)
calnexin, ERp57, calreticulin and tapasin
-help fold MHC I and put it in close proximity to TAP
ERAP1
-trims long peptides to a suitable size for MHC I grooves
endogenous pathway steps
- MHC I, Calnexin and ERp57
- Calnexin leaves, and beta2 microglobulin, tapasin and calreticulin join (PLC)
- Close to TAP
- ERAP trims peptide
- Peptides into groove
>ERp57, calreticulin and tapasin leave