Ch 5

Front 1

Could you discuss the structure of TCR in detail?

Back 1

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

Front 2

What are the similarities and differences between TCR vs. BCR diversity generation?

Back 2

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

Front 3

How does αβ TCR gene rearrangement affect γδ TCR gene rearrangement?

Back 3

delta chain locus is in the middle of the alpha chain locus so if you have rearrangement you will delete the delta chain locus

Front 4

What is the function of MHC?

Back 4

tissue compatiblity
unique in own body
distinguish us from foreign people

Front 5

Can you discuss the structure of MHC class I? MHC class II?

Back 5

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

Front 6

Where does a peptide bind on an MHC molecule and how (peptide characteristics)?

Back 6

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

Front 7

what does TCR bind?

Back 7

needs Ag's to be presented in a certain way,
only binds protein Ag's bound to MHC presented on the APC surface

Front 8

Do you know the sources of peptides for MHC class I vs. II?

Back 8

class one proteins come from inside the cell

class II proteins come from what is continuous with outside of the cell

Front 9

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.

Back 9

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

Front 10

e MHC class II pathway

Back 10

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

Front 11

How are the peptides transported from cytosol to ER for the MHC class I pathway?

Back 11

TAP transporter

Front 12

Which is in excess, peptides or available MHC I or II? Why would this be?

Back 12

more MHC than peptides

Front 13

immunoproteasome subunits

Back 13

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

Front 14

What is the role of the invariant chain?

Back 14

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

Front 15

Can you discuss the stability of a MHC + peptide complex?

Back 15

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

Front 16

Which cell(s) express MHC class I on the cell surface?

Back 16

all nucleated cells (not RBC)

Front 17

Which cell(s) express MHC class II on the cell surface?

Back 17

APC (DC, macrophages, B cells) and thymic epithelial cells

Front 18

Can you discuss polymorphism of MHC?

Back 18

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

Front 19

What are the MHC genes for humans called? Can you name them all?

Back 19

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

Front 20

Can you discuss some examples of immunoevasins?

Back 20

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

Front 21

phases of T cell activation

Back 21

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