Lecture 8: Major Histocompatibility Complex

Question 1

T cells only recognize antigens displayed by ______

Answer 1

MHC complexes on cell surfaces

Question 2

alpha:beta cells recognize antigens as _______

Answer 2

peptide:MHC complexes

Question 3

What to MAIT cells and y: gamma cells recognize?

Answer 3

different types of surface molecules whose expression may indicate infection or cellular stress.

Question 4

What can peptide:MHC complexes signal?

Answer 4

the presence of an intracellular pathogen for elimination by armed effector T cells

Question 5

What happens in dendritic cells?

Answer 5

peptide:MHC complexes serve to activate antigen specific effector T cells

Question 6

What does the structure of the TCR/peptide/MHC complexes look like?

Answer 6

APC > MHC> Antigen> Variable Regions on the end with J alpha and Beta chains in the middle> then connected to the C alpha and beta region> then going to the T cell

Question 7

T Cell receptors recognize antigens in the form of________

Answer 7

a foreign peptide bound to an MHC molecule.

Question 8

What is the Structure of MHC 1:

Answer 8

-3 alpha chains: 2 on the left, 1 on the right which sits above the B2 microglobulin

Question 9

What does MHC 2 structure look like?

Answer 9

2 beta chains on the left and 2 alpha chains on the left.

Question 10

What are the four noncovalent forces involved with MHC?

Answer 10

1. Electrostatic Forces
2. Hydren Bonds
3. Van der Waals forces
4. Hydrophobic forces

Question 11

What are the differences between the distinct subunit compositions of MHC1 and MHC2

Answer 11

MHC1: alpha subunits and closed clefts, ranges from 8-10 amino acids, epitopes in antigen are smaller

MHC2: clefts are open so they are longer peptides

Question 12

MHC 1 binds ______ by both_____

Answer 12

short peptides 8-10 amino acids, both ends

Question 13

Peptides bind to MHC molecules through_____

Answer 13

structurally related anchor residues

Question 14

What is the point of the anchor residues?

Answer 14

They allow for peptide binding stability and specificity of the peptide binding

Question 15

The length of the peptides bound by MHC Class 2 are ______

Answer 15

not constrained, meaning it is much longer

Question 16

Peptides that bind MHC class2 molecules are _______ and their anchor residues lie at _________ from the ends of _____

Answer 16

variable in length, various distances, peptides

Question 17

MHC 2’s variability in length is referred to as ______

Answer 17

open hanging characteristics
- not in the pocket but still involved with receptor interactions

Question 18

What is unique about the dendritic cell?

Answer 18

It is a supercell and is uber presenting

Question 19

Cells become targets of T-cell recognition by ______

Answer 19

acquiring antigens from either the cytosolic or the vesicular compartments

Question 20

Cytosolic Pathogens:

Answer 20

Degrades in: cytosol
Peptides bind to: MHC class 1
Presented to: effector CD8 T cells
Effect on presenting cell: cell death

Question 21

Intravesicular pathogens:

Answer 21

Degrades: endocytic vesicles (low pH)
Peptides bind to: MHC class II
Presented to: Effector CD4 T cells
Effect on presenting cell: activation to kill intravesicular bacteria and parasites

Question 22

Extracellular pathogens and toxins:

Answer 22

Degraded in: endocytic vesicles (low pH)
Peptides bind to: MHC Class II
Presented to: Effector CD4 T cells
Effect on presenting cell: activation of B cells to secrete Ig to eliminate extracellular bacteria/toxins

Question 23

Newly synthesized MHC 1 molecules are retained in _________ until they bind a peptide

Answer 23

the endoplasmic reticulum

Question 24

How is MHC able to exit the ER and go to the cell membrane?

1. Partly fold MHC class I alpha chains bind to __________

Answer 24

calnexin until B2 microglobulins binds

Question 25

How is MHC able to exit the ER and go to the cell membrane? 2. MHC class 1____ complex is released from calnexin, binds a complex of _______ and binds to TAP via tapasin

Answer 25

alpha:b2M complex, chaperone proteins

Question 26

3. Cytosolic proteins and defective ribosomal products are ________ by the proteasome. TAP delivers _______

Answer 26

degraded to peptide fragments, peptides to the ER.

Question 27

4. A peptide binds the MHC class 1 molecules and completes its ______. The MHC Class 1 molecules is released from _______ and exported to ______

Answer 27

folding, the TAP complex, the cell membrane

Question 28

Peptides that bind to MHC II molecules are generated in __________

Answer 28

acidified endocytic vesicles

Question 29

Step 1 of MHC2 generation: 1. Antigen is taken up from _______ to _______

Answer 29

extracellular spaces into intracellular vesicles

Question 30

Step 2 of MHC generation: 2. In early endosomes of neutral pH, endosomal ________

Answer 30

proteases are inactive

Question 31

Step 3 of MHC generation: 3.______ of vesicles actives proteases to degrade antigen into _______ peptide fragments

Answer 31

Acidification, peptide fragments

Question 32

Step 4 of MHC generation: 4. Vesicles containing _____ fuse with vesicles containing ______

Answer 32

peptides, MHC class 2 molecules

Question 33

The invariant chain is ______ CLIP bound to the MHC class II molecules

Answer 33

cleaved to leave a peptide fragment

Question 34

Cleavage steps of invariate chain 1. invariant chain (Ii) binds in the ______ of MHC II molecules

Answer 34

grooves

Question 35

2. II is cleaved initially to leave a fragment bound to the ___________

Answer 35

class II molecule and to the membrane

Question 36

Further cleavage leaves a short peptide fragment, _____ to the class II molecules

Answer 36

CLIP

Question 37

MHC Class II molecules are loaded with _________

Answer 37

peptide in a late endosomal compartment

Question 38

LAMP______

Answer 38

not in the lysosyme and upregulated

Question 39

What does an Adaptor Proteins do?

Answer 39

vesicle formation, cargo selection and sorting

Question 40

Many ______involved in antigen processing and presentation are encoded by _____within the MHC

Answer 40

proteins, genes

Question 41

The protein products of MHC Class I and class II genes are ____________

Answer 41

highly polymorphic

Question 42

MHC polymorphism extends the _________ to which the immune system can reponsd

Answer 42

range of antigens: polymorphism, polygeny,

Question 43

MHC polymorphism affects __________ by T cells influencing both _______and the contacts between _________

Answer 43

antigen recognition, peptide binding, t-cell receptor and MHC molecule

Question 44

The ______ structures of several peptide:MHC:T-cell receptor complexes show a similar orientation of the T cell-receptor over the ________

Answer 44

crystal, peptide:MHC complex

Question 45

Why is there a huge variety of HLA?

Answer 45

They can group together on an internal chain and bind to specific peptides.

Question 46

MHC polymorphism affects ______ by T cells by influencing both peptide binding and the contacts between T_____

Answer 46

antigen recognition, T-cell receptor and MHC molecule

Question 47

Alloreactive cells recognizing _______ are very abundant

Answer 47

non-self MHC

Question 48

The CD4 and CD8 cell-surface proteins of T cells are required to ______________

Answer 48

make an effective response to antigen

Question 49

MHC Class 2 has a ______ interaction with Cd4

Answer 49

beta chain

Question 50

MHC class 1 has a ______ interaction with CD8

Answer 50

alpha chain

Question 51

The _____ family of MHC class 1-like molecules is encoded outside the ______ and presents microbial lipids to ________

Answer 51

CD1, MHC, CD1-restricted T cells

Question 52

The CD1 family of MHC class 1-like molecules is encoded outside ______ and presents microbial lipids to _________

Answer 52

the MHC CD1-restricted T cells

Question 53

Which MHC class molecule is more restricted?

Answer 53

MHC2

Question 54

Dendritic cells are expressed on which classes?

Answer 54

both MHC1 and MHC2

Question 55

B cells are expressed on which classes?

Answer 55

MHC class 1 and 2

Question 56

T cells are expressed more on ____

Answer 56

MHC class 1

Question 57

Neutrophils are expressed on _____

Answer 57

MHC class 1

Question 58

What other nucleated cells are expressed on MHC class 1

Answer 58

hepatocytes, kidney, and brain