Lecture 9: MHC and Antigen Presentation

Question 1

Antigen processing

Answer 1

Generation of peptides from proteins

Question 2

Antigen presentation

Answer 2

Display of processed peptide on cell surface via MHC molecules

Question 3

What are the three types of professional APC’s

Answer 3

Dendritic cells, macrophages and B cells

Question 4

What do MHC I molecules present on

Answer 4

All nucleated cells

Question 5

What do MHC II molecules present on

Answer 5

Antigen presenting cells

Question 6

What type of T cell do dendritic cells present to and what is the response

Answer 6

Naive T cells and results in clonal differentiation and proliferation of effector T cells

Question 7

What type of T cell do macrophages present to and what is the response

Answer 7

Present to effector T cells and results in activation of macrophages- cell mediated immunity

Question 8

What type of T cells do B cells present to and what is the response

Answer 8

Present to effector T cells and result in B cell activation and antibody production-humoral immunity

Question 9

Where are cytosolic pathogens degraded

Answer 9

Cytosol

Question 10

What do cytosolic pathogens bind to

Answer 10

MHC I

Question 11

What are cytosolic presented to

Answer 11

CD8+ T cells

Question 12

What is the effect of presenting cytosolic pathogens to CD8+ T cells

Answer 12

Cell death

Question 13

What are intravesicular pathogens

Answer 13

Pathogens that can survive and replicate inside a phagosome and/or phagolysosome

Question 14

Where are intravesicular pathogens degraded

Answer 14

Endocytotic vesicles with low PH

Question 15

What do intravesicular pathogens bind to

Answer 15

MHC II

Question 16

Where are intravesicular pathogens presented

Answer 16

CD4+ T cells

Question 17

What is the effect of presenting intravesicular pathogens to CD4+ T cells

Answer 17

Activation to kill intravesicular bacteria

Question 18

What are extracellular pathogens

Answer 18

Bacteria growing outside of cell, viruses not yet in target cell. They can be bound by BCR and endocytosed

Question 19

Where are extracellular pathogens degraded

Answer 19

Endocytotic vesicle with low Ph

Question 20

What do extracellular pathogens bind to

Answer 20

MHC II

Question 21

Where are extracellular pathogens presented

Answer 21

CD4+ T cells

Question 22

What is the effect on presenting extracellular pathogens to CD4+ T cells

Answer 22

Activation of B cells to secrete Ig to eliminate bacteria/toxins

Question 23

What is the messenger between innate and adaptive immunity

Answer 23

Dendritic cell

Question 24

How do dendritic cells sample environment

Answer 24

TLR’s

Question 25

When dendritic cells bind an antigen what is unregulated and for what purpose

Answer 25

Upregulate CD molecules to initiate T cell binding- differentiates CD8+-Tc and CD4+-Th

Question 26

What are the variable regions on MHC I molecule

Answer 26

Alpha-1 and alpha-2

Question 27

What are the components of MHC I structure

Answer 27

Alpha-1, alpha-2, B2-microglobulin

Question 28

Where are the variable regions on MHC II

Answer 28

Beta-1

Question 29

What is the structure of MHC II molecule

Answer 29

Alpha-1, alpha-2, beta-1, beta-2

Question 30

All MHC molecules must be bound to a peptide to be ______

Answer 30

Expressed on the cell surface, when not bound will be broken down empty MHC molecule not on surface

Question 31

Any ___ processed into a peptide can bind into the ____ and be presented to a T cell

Answer 31

Any protein- self or non-self MHC groove

Question 32

MHC restricted T cells respond mainly to lipids, carbohydrates, sugars, or proteins

Answer 32

Proteins broken down into peptides

Question 33

If T cell binds high affinity with MHC + peptide then what happens

Answer 33

T cell activation

Question 34

What type of peptides do MHC I molecules bind and what type of T cell do they present to

Answer 34

Bind endogenous peptides and present to CD8+ T cells

Question 35

What type of peptides do MHC II molecules bind and what type of T cell do they present to

Answer 35

exogenous and CD4+ T cells

Question 36

Where are MHC I molecules translated to and fold

Answer 36

ER, they don’t see antigens in cytosol

Question 37

What protein is responsible for carrying in amino acid strands to MHC I

Answer 37

Transporter proteins (TAP)

Question 38

What is a proteasome

Answer 38

Degrades proteins into peptides

Question 39

What increases the rate of proteolysis

Answer 39

INF-gamma

Question 40

The increase rate of proteolysis ____likelihood that antigenic peptides escape this processing

Answer 40

Increases

Question 41

___transports peptides to TAP

Answer 41

Chaperones

Question 42

Describe the steps in the MHC I Antigenic Peptide Generation

Answer 42

Partly folded MHC I alpha chain will bind calnexin while waiting for B2m Alpha-B2m binds and releases calnexin and binds chaperones and TAP via tapasin Cytosolic proteins and defective ribosomal products are degraded into peptides via proteasome. TAP delivers peptides to ER Peptide binds MHC and completes folding, MHC is released from TAP and exported to cell membrane

Question 43

What are immunoevasins

Answer 43

Allow viruses to evade antigen presentation by blocking TAP functions, block antigenic peptide loading into MHC, can tag MHC molecules for degradation

Question 44

What do US6 and ICP47 do

Answer 44

They are immunoevasins that block TAP and prevent antigen from moving from cytosol to ER to bind MHC

Question 45

What is adenovirus protein E19

Answer 45

Immunoevasins that disrupts tapasin binding to MHC molecule and inhibits antigenic peptide loading

Question 46

What is Mk3

Answer 46

E3-ubiquitin ligase that targets MHC I for degradation

Question 47

What are some examples of organisms that replicate in vesicles in macrophages

Answer 47

Leishmania, mycobacterium and salmonella

Question 48

What are intravesicular bacteria not exposed to and what must then degrade proteins

Answer 48

Cytosolic proteasome so intravesicular proteases degrade proteins

Question 49

Describe steps of MHCII and intravesicular bacteria

Answer 49

Antigen is taken up from extracellular space into intravesicular vesicle In early endosomes pH is neutral so proteases are inactive Acidification of vesicles activates proteases to degrease peptides to proteins Vesicles containing peptide fuse with vesicle containing MHC II

Question 50

What does the invariant chain prevent

Answer 50

Binding to self antigens

Question 51

Describe the steps of MHC II antigenic prep for endocytosed/BCR bound antigens

Answer 51

Invariant chain forms complex with MHC blocking binding of self peptides, misfolded proteins Invariant chain is cleaved in acidified endosome and leaves short peptide called CLIP bound to MHC. Endocytosed antigens are degrade into peptides but CLIP is still blocking their binding to MHC HLA-DM binds to MHC II releasing CLIP and allowing other peptides to bind MHC II. MHC II then travels to cell surface

Question 52

What is the role of HLA-DM and where is it found

Answer 52

Role: catalyzes loading of antigen into MHCII binding pocket Found: only in MHC II compartment

Question 53

Cross presentation and activation of naive CD8 T cells

Answer 53

Some dendritic cells present on their MHC I molecules

Question 54

What is the source of protein antigens in MHC II pathway?

Answer 54

Endosomal/lysosomal proteins- internalized from extracellular environment

Question 55

What is the source of protein antigens in MHC I pathway

Answer 55

Cytosolic proteins- mostly synthesized in cell

Question 56

What are the enzymes responsible for peptide generation in MHC II pathway

Answer 56

Endosomal and lysosomal proteases

Question 57

What enzymes are responsible for peptide generation in MHC I

Answer 57

Enzymatic components of cytosolic proteasome

Question 58

What is the site of peptide loading of MHC II pathway

Answer 58

Late endosomes and lysosomes

Question 59

What is the site of peptide loading in MHC I

Answer 59

Endoplasmic reticulum

Question 60

What molecules are involved in transport of peptides and loading of MHC molecules in MHC II pathway

Answer 60

Invariant chain and HLA-DM

Question 61

What molecules are involved in transport of peptides and loading of MHC molecules in MHC I pathway

Answer 61

TAP

Question 62

How are MHCs able to bind so many antigens

Answer 62

Genetic diversity with many different loci

Question 63

What are the loci in MHC I and what do they encode for

Answer 63

HLA-A, B, C and encode for alpha chain

Question 64

What are the loci in MHC II and what do they encode for

Answer 64

HLA-DP, DQ, DR and encode for alpha and beta chains

Question 65

Polymorphic

Answer 65

Multiple alleles for each gene

Question 66

What is a HLA haplotype

Answer 66

Set of MHC alleles present on each chromosome

Question 67

Each person has __ HLA haplotypes

Answer 67

2

Question 68

Professional APC’s expresses alleles of which class (es)

Answer 68

MHC I and II

Question 69

All nucleated cells express which class (es)

Answer 69

MHC I

Question 70

The diversity of MHC alleles expressed partially determines individuals susceptibility to _____

Answer 70

Infectious diseases

Question 71

Is it advantageous to be MHC heterozygote or homozygote

Answer 71

Heterozygote can respond to greater number of antigens

Question 72

There has been linkage between expression of certain DLA haplotypes and susceptibility to what diseases

Answer 72

Canine RA, I-M hemolytic anemiadiabetes mellitus

Question 73

Association between expression of certain BoLA alleles and resistance to what has been shown

Answer 73

Resistant to bovine leukosis due to infection with bovine leukemia virus

Question 74

What are superantigens

Answer 74

Toxins that encourage the aberrant binding of MHC and TCR results in long lived binding and cytokine storm