Adaptive immunity 3

Question 1

Why do T cells need antigen presentation?

Answer 1

Unlike B cells, T cells do not recognise native antigens

Question 2

Activation of T cells

Answer 2

Antigen presenting cells (APCs) determine which peptides will be presented on class I and class II MHC during initial activation

T cells need to be able to distinguish between external antigens (taken up by APCs) and internal antigens (infected cell)

Question 3

What is antigen processing?

Answer 3

Enzymatic process of degrading proteins through proteases into antigenic peptides

Antigen processing requires energy (ATP) and movement of endocytic vesicles

Question 4

Two antigen processing pathways

Answer 4

Endogenous antigens in cytosol presented on class I MHC molecules to CD8+ T cells

Exogenous antigens in endosomes presented on class II MHC molecules to CD4+ T cells

Question 5

Endogenous antigens: generation of class I MHC peptides

Answer 5

Endogenous antigens are from proteins produced inside the cell

These includes self protein antigens and foreign protein antigens

Class I MHC antigens activate cytotoxic CD8 T cells for killing infected cells and tumour cells

Question 6

Endogenous antigens: proteasome

Answer 6

Proteasome unfolds proteins and then cleaves proteins into peptides and amino acids

Peptides produced in the cytosol are transported into the endoplasmic reticulum

Question 7

Endogenous antigens: TAP proteins

Answer 7

TAP 1 and TAP 2 form heterodimer in membrane of ER to facilitate selective transport of peptides from cytoplasm into lumen of ER

TAP pump preferentially transport peptides with a length of 8-15 amino acids

Question 8

CD8+ Tc activated by endogenous or intracellular antigens

Answer 8

Effector CD8+ Tc (CTLs) are primarily needed for the eradication of infected cells

CTLs can also be activated against cancer cells (tumour) targets ‘neo antigens’

Question 9

CTL killing of infected target cells

Answer 9

Viruses must replicate inside cells and many bacteria and parasites live inside host cells

Therefore antigens for stimulating CTLs come from inside the cell because they signal an intracellular infection

Question 10

Immune evasion

Answer 10

Viruses can interfere with class I MHC expression to escape killing by CTLs

Herpes simplex virus (HSV) protein ICP47 can selectively bind to TAP and inhibit the transfer of peptides into ER

Question 11

How are peptides generated?

Answer 11

Antigen is taken up into intracellular vesicles

In early endosomes of neutral pH, endosomal proteases are inactive

Acidification of vesicles activates proteases to degrade antigen into peptide fragments

Vesicles containing peptides fuse with vesicles containing MHC class II molecules

Question 12

Trafficking of MHC class II molecules

Answer 12

MHC class II a and B chains associate in the ER

In the trans golgi network, MHC class II is sorted into vesicles

These vesicles deliver MHC class II to specialised compartments where peptide loading occurs

Question 13

HLA-DM

Answer 13

Acts like a chaperone for MHC class II molecules and catalyses the release of CLIP once an antigenic peptide is present

Question 14

Exogenous pathway: class II MHC peptide loading

Answer 14

Class II MHC loading takes place in endosomes where acidic pH is required for protein degradation into peptides

Invariant chain is degraded and CLIP is exchanged with foreign peptide

Question 15

CD4+ Th activation by exogenous antigens

Answer 15

Foreign antigens/ extracellular pathogens need to be taken up by APCs to get noticed by Th cells of the immune system

This leads to activation of macrophage and the production of secreted antibody by plasma cells

Question 16

Viral inhibition of class II MHC

Answer 16

Adenovirus interferes with class II upregulation in APCs

The HSV viral envelope protein, glycoprotein B, reduces MHC class II processing and inhibits the production of invariant chain peptide

HIV interferes with class II processing

Question 17

Pathogens that evade lysosomes

Answer 17

Leishmania and mycobacteria (tuberculosis) prevent phagosome- lysosome fusion

Question 18

How are T cell antigens kept apart?

Answer 18

Location

Class I and class II MHC molecules both traverse through ER to cell surface but load peptides in different cell compartments

Control is through accessory proteins

• class I requires TAP, tapasin, etc control
• control II requires low pH for removal of li

Question 19

Exogenous antigens

Answer 19

From external compartment

Have lots of different types of receptors on their surface

Form phagolysosome

Question 20

Endogenous antigens

Answer 20

Cell that have already been invaded by pathogens

Commonly enter cells and try to hijack machinery of cells to make more copies of themselves

Question 21

Proteasome

Answer 21

Recognises and processes foreign antigens

Question 22

CD8+ T cells

Answer 22

Cytotoxic

Eradicate cells that have been invaded by viruses or bacteria

Eradicate cancer cells - neoantigen - recognised as non-self