Quiz 4 Part 2

Question 1

Explain in detail the structure of MHC Class 1

Answer 1

MHC class 1 consists of an alpha transmembrane chain with 3 alpha subunits

alpha 1 and alpha 2 = peptide binding domains

alpha 3 — supporting, immunoglobulin like domain

support (accessory) protein small, Ig like === beta 2 microglobulin

Question 2

explain in detail the structure of MHC Class 2

Answer 2

has alpha and beta transmembrane chains
4 subunits total, each contributing to the peptide binding domain and supporting domains

Question 3

explain where the peptide binding site is on an MHC molecule (both class 1 and class 2)

Answer 3

the binding site sits in a deep groove on the surface of the MHC molecule

Question 4

is peptide binding to MHC covalent or noncovalent?

Answer 4

non-covalent forces

Question 5

MHC class 1 can bind which peptides?
What about class 2?

Answer 5

MHC class 1 binds peptides of 8-10 amino acids (usually a 9mer)

MHC class 2 binds peptides of 13-26 amino acids

Question 6

MHC molecules have a ____ binding specificity, meaning what?

Answer 6

PROMISCOUS

meaning that MHC molecules can bind a variety of peptides with differing amino acid sequences (derived from the degradation of pathogens)

Question 7

explain the binding of TCR binding to MHC on MHC Class 1

Answer 7

the CD8 coreceptor on the CD8+ T cell binds to the a3 domain on MHC class 1

Question 8

explain the bonding of TCR to MHC on class 2 MHC

Answer 8

the CD4 coreceptor in the CD4 T cell binds the B2 domain of MHC class 2

Question 9

MHC class 1 molecules bind peptides in…..

Answer 9

the ER

Question 10

MHC class 2 molecules bind peptides in….

Answer 10

endosomes

Question 11

MHC class 1 molecules bind _______peptides in the ER

Answer 11

non self (derived from intracellular pathogens)

Question 12

in the presence of infection, the proteasome in the cell is altered in response to…….

Answer 12

IFNY (secreted by NK cells)

Question 13

when the proteasome is altered by IFNY, what is happening to it?

Answer 13

the modified proteasome processes peptides that are likely to bond to MHC Class I

Question 14

the modified proteasome due to IFNY (produced by NK cells) is called……

Answer 14

an immunoproteasome

Question 15

in the ABSENCE of infection, what is the proteasome called and what is it doing?

Answer 15

called a constitutive proteasome.
always actively processing SELF proteins

Question 16

How are peptides transported to the ER to be recognized by MHC Class 1?

Answer 16

peptides are transported from the immunoproteasome to the ER by an ATP-dependent transporter protein called TAP

Question 17

does TAP require ATP?

Answer 17

yes

Question 18

where are MHC class 1 molecules assembled?

Answer 18

in the ER

Question 19

what aids the assembly of MHC class 1 molecules?

Answer 19

chaperone proteins
Calnexin stables the alpha heavy chain until B-2microglobulin binds

Question 20

explain the full process of MHC Class 1 binding a peptide from an intracellular pathogen

Answer 20

MHC Class 1 molecule is assembled. Calnexin is a chaperone protein that aids in this process by stabilizing the alpha heavy chain until B-2microglobulin binds

when the binding of b2-microglobulin to the alpha heavy chain is finished, calnexin is released.

the MHC class 1 molecule then joins the peptide loading complex consisting of 3 proteins.

a peptide is delivered by TAP (a transporter) to the class 1 heavy chain. this binding of peptide to MHC Class 1 forms the MATURE MHC CLASS 1 MOLECULE. it undergoes a conformational change

the class 1 molecule then dissociates from the peptide loading complex and is exported from the endoplasmic reticulum in a vesicle

Question 21

do most peptides exhibit tight binding?

Answer 21

no

Question 22

some peptides are ____ and some peptides are ____ to create better binding

Answer 22

some peptides are REJECTED and some peptides are EDITED to create better binding

Question 23

what enzyme chews away the ends of peptides to reduce their size and make them fit better into MHC?

Answer 23

ERAP (endoplasmic reticulum aminopeptidase)

Question 24

explain the process of ERAP

Answer 24

MHC Class 1 is loaded with peptide that is too long at the N terminus
ERAP removes N-terminal amino acids to give a peptide of 8-10 residues
MHC class 1 molecule then travels to the cell surface via a vesicle

Question 25

Which peptides bind to MHC Class 2 proteins?

Answer 25

peptides that are produced in phagolysosomes
(from extracellular pathogens – phagocytosis)

or

receptor mediated internalization (endocytosis)

Question 26

where are MHC class 2 molecules assembled?

Answer 26

also in the ER, but the INVARIANT CHAIN prevents ER peptides from binding to class 2 (they’re meant for class 1)

Question 27

what is the final destination of MHC class 2 molecules? how do they get there?

Answer 27

MHC class 2 proteins want to fuse with a phagolysosome.

MHC class 2 molecules are produced in the ER. They are secreted in vesicles from the golgi and eventually fuse with a phagolysosome in the cytosol

Question 28

MHC vesicles are also called….

Answer 28

MHC class 2 compartments OR MIICs

Question 29

what activates proteases to cut up the antigen in a phagolysosome?

Answer 29

acidification

Question 30

when and how is the invariant chain on MHC class 2 cleaved?

Answer 30

Once MHC class 2 is in a vesicle, the invariant chain is cleaved, LEAVING THE CLIP FRAGMENT BOUND.

once the MIIC fuses with a phagolysosome, HLA-DM facilitates the release of clip, allowing the peptides to bind to MHC Class 2

Question 31

what removes CLIP?

Answer 31

HLA-DM

Question 32

what antagonizes the function of HLA-DM?

Answer 32

HLA-DO

Question 33

the balance of HLA-DM vs HLA-DO activity is regulated by……

Answer 33

cytokines

Question 34

can HLA-DM bind peptide?

Answer 34

no

Question 35

where is HLA-DM concentrated?

Answer 35

in MIIC

Question 36

What is the function of HLA-DM?

Answer 36

to aid in peptide loading by inducing conformational changes in the groove of the peptide binding site, releasing CLIP

Question 37

What released HLA-DM?

Answer 37

the tight binding of stable peptide to the MHC Class 2 protein

Question 38

cytotoxic T cells are activated by….

Answer 38

virus infected cells (MHC Class 1)

Question 39

how are naive T cells recruited to the site of infection?

Answer 39

by activation of APC’s (antigen presenting cells)

Question 40

explain how the MHC Class 2 pathway material can be transferred to MHC class 1 pathway

what is the term for this?

Answer 40

antigens can leech out of the phagolysosome and get into the cytosol. they then become immunoproteasome material and shunt into the class 1 pathway

this is termed cross presentation

Question 41

are neutrophils more involved in the MHC class 1 or class 2 response?

Answer 41

class 1

bc viruses infect just about any cell
neutrophils are more involved in the early innate response, so they’re not in the class 2 pathway

Question 42

which cells express MHC class 2

Answer 42

b cells and dendritic cells the most
then macrophages
then T cells

Question 43

explain the contact of T cell receptor with MHC complex

Answer 43

the T cell receptor contacts BOTH peptide side chains, and MHC itself

binding occurs at CDR loops