Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
21 Cards in this Set
- Front
- Back
Could you discuss the structure of TCR in detail?
|
composed of two chains (alpha and beta - class I) or (gamma and delta - class II)
each chain has a variable region and a constant region held together with disulfide bonds TCR associates with CD3 and zeta chains - CD3 and zeta chains send the signal down to the sycosol after TCR binds Ag |
|
What are the similarities and differences between TCR vs. BCR diversity generation?
|
TCR diversity generation
Similarities to Ab diversity (variable region) - Multiple V, (D), J genes - RSS and 12/23 rule applies. - Same enzymes carry out the gene recombination - Also junctional diversity Different than Ab diversity - No somatic hypermutation - TCR does not have the equivalent of the Ab heavy chain constant region diversity - No secretion of TCR |
|
How does αβ TCR gene rearrangement affect γδ TCR gene rearrangement?
|
delta chain locus is in the middle of the alpha chain locus so if you have rearrangement you will delete the delta chain locus
|
|
What is the function of MHC?
|
tissue compatiblity
unique in own body distinguish us from foreign people |
|
Can you discuss the structure of MHC class I? MHC class II?
|
Class II:
-two chains -three alpha domains -one beta micro globulin domain -a1 and a2 make up the Ag binding site -b sheet on floor of peptide binding groove - on side you get two alpha helicies class II: -two chains -two alpha and two beta domains -beta1 and alpha1 form Ag binding site |
|
Where does a peptide bind on an MHC molecule and how (peptide characteristics)?
|
peptides bind in the peptide binding groove
inside the hot dog bun hydrogen bonding - side chains interact with the peptide class I binds small AA peptides class II is more lenient on size |
|
what does TCR bind?
|
needs Ag's to be presented in a certain way,
only binds protein Ag's bound to MHC presented on the APC surface |
|
Do you know the sources of peptides for MHC class I vs. II?
|
class one proteins come from inside the cell
class II proteins come from what is continuous with outside of the cell |
|
Can you describe the process of protein degradation and presentation by the MHC class I pathway? Include all proteins (enzymes, etc) involved in the process.
|
a virus infects a cell
viral proteins synthesized in the cytosol peptide is cut up by PROTEASOME unbound MHC class I is stabilized by CALNEXIN (chaperone protein) until beta2 - microglobulin binds calnexin is released MHC class I forms the peptide loading complex with a bunch of proteins including TAP peptide fragments are shuttled to the ER via TAP transporter (requires ATP) peptide fragments of viral proteins bound by MHC in the ER sometimes the peptide is too long so ERAP removes AA from peptide the class I molecule dissociates from the peptide loading complex and is exported from the ER bound peptides transported by MHC class I to the cell surface |
|
e MHC class II pathway
|
Ag 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 Ag into peptide fragments invariant chain blocks binding of peptides to MHC class II molecules in the ER, in vesicles invariant chain is cleaved, leaving the CLIP fragment bound vesicles containing peptides fuse with vesicles containing MHC class II molecules , CLIP blocks binding of peptides to MHC class II in vesicles, HLA-DM facilitates peptides to bind |
|
How are the peptides transported from cytosol to ER for the MHC class I pathway?
|
TAP transporter
|
|
Which is in excess, peptides or available MHC I or II? Why would this be?
|
more MHC than peptides
|
|
immunoproteasome subunits
|
proteins that are necessary for peptide generation, genes in the MHC locus, subunit of proteosome is changed so that it cleaves proteins that will fit really well into the MHC
creation is triggered by cytokines LMP2 and LMP7 MECL-1 is not in MHC locus PA-28 : goes next to the proteasome that help let the peptide out of the proteasome |
|
What is the role of the invariant chain?
|
binds in the groove of MHC class II molecule
without the invariant chain MHC class II is retained in the ER Invariant chain guides MHC II to endosomal compartment |
|
Can you discuss the stability of a MHC + peptide complex?
|
very stable - need peptide to be sitting in the peptide binding groove of MHC for it to be stable
peptide will sit very tightly once its at the cell surface the peptide isnt going anywhere |
|
Which cell(s) express MHC class I on the cell surface?
|
all nucleated cells (not RBC)
|
|
Which cell(s) express MHC class II on the cell surface?
|
APC (DC, macrophages, B cells) and thymic epithelial cells
|
|
Can you discuss polymorphism of MHC?
|
many allelic variation in a population at each gene
for example: for the HLA-A gene, theres actually lots of possibilities per gene locus per chromosome |
|
What are the MHC genes for humans called? Can you name them all?
|
human leukocyte antigen (HLA)
HLA class I: three genes: HLA-A, HLA-B, HLA-C HLA class II: three genes: HLA-DP, HLA-DQ, and HLA-DR |
|
Can you discuss some examples of immunoevasins?
|
alot of viral proteins that function to evade the MHC class I
viral protein IPC47 or US6 associate with TAP and block TAP from transporting peptides (occurs in herpes simplex) viral protein E19 inhibits peptide loading onto MHC class I proteins US11 causes dislocation of MHC class I molecules back into the cytosol for degradation |
|
phases of T cell activation
|
1. activation phase
---APC/DC presents MHC class I - peptide complex, binds TCR on CD8 T cell ---APC/DC presents MHC class II -peptide complex that binds to TCR on CD4 t cell 2. Proliferation phase 3. differentiation phase 4. effector phase --nucleated cell presents MHC class I - peptide complex that binds to TCR on CD8 presenting -CTL ---DC/APC/B cell/macrophage presents MHC class II - peptide complex that binds to TCR on CD4 presenting - Helper T/T reg cell |