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Immunity, Infection and Disease > Antigen Exposure, Processing, and Presentation > Flashcards

Antigen Exposure, Processing, and Presentation Flashcards

1
Q

What inspects antigens presented by MHC class 1?

A

CD8+ T cells

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2
Q

What inspects antigens presented by MHC Class 2?

A

CD4+ T cell

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3
Q

What do CD4+ and CD8+ T cells do in response to seeing an antigen?

A

CD8+ T cell - kill cell and emit cytokines, CD4+ T cell - emit cytokines

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4
Q

2 phases of antigen presenting

A

Priming and effector phases

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5
Q

What is the major basis for transplanted tissue rejection?

A

MHC incompatibility

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6
Q

What presents lipid-based antigens?

A

CD1

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7
Q

Lengths of peptides presented by Class 1a and Class 2 MHCs

A

Class 1a - 8 to 10 AAs, Class 2 - 13 to 17 AAs

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8
Q

What cell recognizes antigens presented by QE?

A

Regulatory CD8+ T cells, NK cells

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9
Q

What classifies type I MHC molecules?

A

They all bind B2 microglobulin and all have three globular domains and a heavy chain

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10
Q

What molecules make up MHC Class 1B?

A

M3 (mouse), QE, and CD1

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11
Q

What peptide fragments that can be presented from antigens?

A

Proteosomes

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12
Q

What type of proteosomes take up ubiquitilated proteins?

A

Proteosomes with a 19S at either end

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13
Q

What proteins act on degraded proteins between the proteosome and delivery to ER?

A

Cytosolic peptidases

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14
Q

How are degraded antigenic peptides delivered from cytosol (post-proteasome) to ER (where MHC will pick them up)?

A

By active transport via TAP (Transporter of Antigen Peptides

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15
Q

Once an antigen fragment arrives in the ER, what cleaves it further?

A

ERAAP (ER-associated Aminopeptidase)

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16
Q

Which end of an antigen fragment can be modified by ERAAP?

A

Only the N-terminus (the proper C-terminus has to be created in the cytosol before arrival in ER)

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17
Q

What happens to antigens that are initially delivered to the ER?

A

They get retrotranslocated into the cytosol, run through the proteosome, then delivered back to ER

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18
Q

What is the difference in the peptide binding groove between Class I and Class II MHC molecules?

A

Class II has an open ended binding cleft (you dont need peptides of a specific length)

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19
Q

Which class of MHC molecules requires antigen degradation before it can present and why?

A

Class I, because it is not open-ended (theoretically Class II can bind any length antigen)

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20
Q

Where do MHC Class II molecules meet their antigens?

A

In the endosomal/phagosomal compartment

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21
Q

Why arent MHC class II proteins degraded with their antigens?

A

Because MHC is highly resistant to proteases

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22
Q

What allows Class II MHC to leave the ER?

A

Binding of an invariant chain

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23
Q

Invariant chain

A

A 216 AA type II glycoprotein which assembles with Class II MHCs in the ER

24
Q

How do MHC Class IIs and Invariant chains get to the endosome and how do they get separated once they are there?

A

Invariant chain has a tail sequence which directs the complex to late endosomes. Invariant chain is highly susceptible to proteolysis, but MHC Class II is highly resistant

25
Q

What prevents other peptides from binding MHC Class II before it reaches the endosome?

A

The CLIP sequence of the invariant chain (which gets separated from the MHC in the endosome)

26
Q

What endosomal protease destroys disulfide bonds?

A

GILT (gamma-interferon inducible lysosomal thiol reductase)

27
Q

What removes invariant chains CLIP sequence from MHC class II proteins and loads the antigen?

A

H-2M (mouse) or HLA-DM (man)

28
Q

Why do MHC class Is bind to CD8+ T cells and Class IIs to CD4+ T cells and where on each MHC does the relevant receptor attach?

A

Class Is have CD8 receptors on their A3 domain, Class IIs have CD4 receptors on their B2 domain

29
Q

What types of cells express MHC class I?

A

All cells except RBCs (but low expression on hepatocytes, kidney, and brain)

30
Q

Which MHC class is expressed in more cell types?

A

MHC Class I. Class II is mainly dendritic cells, macrophages, and B cells (overactivation can be a problem)

31
Q

Dendritic cells

A

Take up material non-specifically at sites of inflammation by macropinocytosis and then migrate to lymph nodes and spleen for presentation to T cells

32
Q

Macrophages

A

Harbor intracellular organisms, presentation to T cells results in release of factors that activate the macrophage

33
Q

What causes cells to express Class II MHCs during an immune response

A

Gamma-interferon

34
Q

What type of cell can undergo cross-presentation and what does this mean?

A

Dendritic cells. This is where they phagocytose an infected cell so their own MHC Class I can get access to antigen to present (antigen has to enter DCs cytosol)

35
Q

Why is cross-presentation especially useful?

A

Because many pathogens have developed strategies for inhibiting class I processing, but DC cross-presentation escapes such inhibition

36
Q

What are the loci of the MHC class II gene in humans and which one has the most variability?

A

DP, DQ, DR (DR is most variable)

37
Q

Superantigens

A

Cause non-specific activation of a huge number of T-cells

38
Q

What are the three professional Antigen Presenting Cells (APCs) and what MHC class do they always use?

A

Dendritic cell, Macrophage, and B cell. Always use Class II

39
Q

What conformations of antigen do B cells and T cells respectively react to?

A

B cells - native, folded antigen, T-cells - antigen fragments

40
Q

How is the T-cell response to mycobacterial infection different?

A

In mycobacterial infections, parasitized macrophages present pathogen-derived peptides to CD4+ T-cells (not CD8+), which incite them to carry out more efficient killing of pathogen

41
Q

Which MHC class can present superantigens?

A

Class II only

42
Q

What polypeptide chains compose MHC Class I molecules?

A

Heavy chain (A1, A2, A3 plus transmembrane domain and tail), and B2-microglobulin (one IG-like domain non-covalently associated with the heavy chain)

43
Q

Where is the peptide binding groove on MHC class 1 molecules?

A

At the interface between the A1 and A2 domains

44
Q

Is the antigen presenting system quiet in uninfected cells?

A

No, it is constitutively active. For uninfected cells, it is presenting normal improperly folded proteins or those that are turned over as part of normal upkeep

45
Q

What polypeptide chains compose MHC Class 2 molecules?

A

Alpha and B (each roughly same size with transmembrane portions)

46
Q

Where is the peptide binding groove in MHC Class 2 molecules?

A

Between the A1 and B1 domains

47
Q

What type of antigen cannot be readily absorbed by dendritic cells via cross-presentation?

A

Soluble antigens

48
Q

What is another name for MHC in humans?

A

Human Leukocyte Antigen

49
Q

How many class I heavy chain genes does each person have?

A
  1. Three (A,B,C) on each chromosome
50
Q

How many different MHC class II molecules can be expressed and how many alleles are these from?

A

12 different MHC class II molecules from 3 alleles (HLA-DP, HLA-DQ, HLA-DR)

51
Q

Also encoded in the MHC Class 2 region of the genome are genes for what?

A

TAP and two proteasomal subunits

52
Q

In what part of the MHC molecule is most variation found (within the population)?

A

In the peptide binding pocket region

53
Q

Which MHC class alleles have a stronger link with autoimmune diseases?

A

Class II

54
Q

What molecules bind superantigens and where do they bind?

A

Superantigens bind to the outside of MHC Class II molecules

55
Q

What does HLA-E activate, what does it bind, and what type of MHC is it?

A

MHC Class 1b, activates CD8+ T cells and NK cells, binds B2M and peptides from bacterially-derived HSPs

56
Q

What is CD1 and what does it respond to?

A

A non-MHC-encoded molecule which presents mycolic acid and lipoarabinomannan (cell wall components) from Mycobacteria

Immunity, Infection and Disease (86 decks)

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