module 04 section 02 (antigen processing/presentation) Flashcards
what does antigen processing involve?
protein degradation and formation of the peptide:MHC complex
endogenous antigens are processed through which pathway?
cytosolic
exogenous antigens are processed through which pathway?
endocytic
the cytosolic pathway results in the formation of which class of MHC:peptide complex?
MHC class I
the endocytic pathway results in the formation of which class of MHC:peptide complex?
MHC class II
what does antigen presentation involve?
the transport of peptide:MHC complexes to the cell membrane of the APCs where they’re displayed to T-cells
peptide:MHC class I complex is presented by what cells?
all nucleated cells
peptide:MHC class I complex is recognized by what cells?
CD8+ cytotoxic T-cells
peptide:MHC class II complex is presented by what cells?
professional APCs
peptide:MHC class II complex is recognized by what cells?
CD4+ helper T-cells
“endogenous antigens” refers to the fact that the antigen originates where?
inside the cell (i.e. can be self or foreign proteins)
foreign endogenous antigens can include: (2)
viruses, intracellular bacteria from infected host cells
what are cytosolic proteins degraded by?
a large multicatalytic protease complex (proteasome) encoded by the LMP genes
describe the degradation of cytosolic proteins
the proteasome generates peptide fragments in the cytosol, which are then transported to the ER, where they bind to MHC class I molecules
what does the cytosolic antigen processing pathway lead to? in how many steps?
- the expression of a peptide:MHC class I complex on the cell surface
- 5
what is step 1 of the cytosolic pathway?
(start in the lumen of the ER)
- newly synthesized MHC class I α chain rapidly binds to molecular chaperone calnexin
- this maintains a partially folded state of the α chain in the ER
- β2 microglobulin binds to the α3 chain
what is step 2 of the cytosolic pathway?
- MHC class I α:β2m complex is released from calnexin and binds to calreticulin and tapasin
- tapasin functions to bring the TAP transporter to the MHC complex (to form peptide loading complex)
what is a TAP transporter?
TAP1 and TAP2: -these are ATP-binding cassette proteins involved in transporting short peptides from the cytosol into the lumen of the ER, where they associate with MHC class I molecules
what is step 3 of the cytosolic pathway?
- peptide fragments from proteasome degredation in the cytosol are transported into the ER via the TAP transporter
- calreticulum bound to the MHC molecule, makes the binding groove accessible for peptide binding as it partially unfolds the molecule
mutations in the TAP1 or TAP2 genes results in what?
prevents antigen presentation by MHC class I molecules bc the peptide cannot be transported into the ER
what is the result of the lack of antigen presentation via MHC class I
the inability to activate CD8+ cytotoxic T-cells (likely that they’re more susceptible to infection)
what is step 4 of the cytosolic pathway?
- once the peptide:MHC class I complex is formed, it dissociates from the calreticulin, tapsin, and TAP
- the complex is exported from the ER to the golgi apparatus via vesicle transport
what is step 5 of the cytosolic pathway?
- the peptide:MHC class I complex is transported to the cell surface
- here these complexes can be recognized by T-cell receptors on cytotoxic T-cells
what is “peptide editing”?
when a peptide binds to the MHC complex during the cytosolic pathway, but is unstable, so the complex releases it
“exogenous antigen” refers to the fact that the antigen originates where?
from oustide the cell
exogenous antigens can include: (3)
extracellular bacteria, toxins, proteins
how can exogenous antigens be internalized? (3)
by professional APCs, receptor-mediated endocytosis, or both
what are endocytic proteins degraded by?
endosomes - acidified vesciles
what does the endocytic pathway lead to? in how many steps?
- the expression of a peptide:MHC class II complex on the cell surface
- 5
what is step 1 of the endocytic pathway?
partially folded MHC class II molecule (which assembles in the ER) is bound by the invariant chain in the ER
what is the function of the invariant chain?
blocks endogenous peptides from binding to MHC class I in ER
what is step 2 of the endocytic pathway?
- the invariant chain facilitates export of MHC class II molecules from the ER through the golgi apparatus
- at this point it will leave the golgi in an endosome
what is step 3 of the endocytic pathway?
- internalized antigens within endocytic compartments fuse with the endosome containing MHC class II molecules
- the invariant chain is digested by proteolytic enzymes within the endosome, leaving behind a short fragment called CLIP, that remains bound to MHC class II molecules
what is step 4 of the endocytic pathway?
- HLA-DM removes CLIP, making the binding cleft of the MHC class II molecule accessible
- also catalyzes the binding of pathogenic peptides to the MHC class II molecule
what is step 5 of the endocytic pathway?
- the peptide:MHC class II complex is transported to the cell surface
- here these complexes can be recognized by T-cell receptors on helper T-cells
the cytosolic pathway is involved in ___ immunity?
cell-mediated
the endocytic pathwat is involved in ___ immunity?
humoral
