Antigen Presentation

Question 1

What is antigen presentation?

Answer 1

Process by which cells display peptide fragments of antigens to T cells;
engaging in the adaptive immune system
With specificity, diversity, memory and self/non self discrimination

Question 2

MHC molecules

Answer 2

MHCI and II
Polygenic and polymorphic
Allows immune system to respond to wide range of antigens
Polymorphism occurs at peptide binding sites and TCR contact sites

Question 3

MHC I is recognised by..

Answer 3

CD8+ - cytotoxic T cells

Question 4

MHC II is recognised..

Answer 4

CD4+ - T helper cells

Question 5

MHC I is a source of what type of protein?

Answer 5

Cytosolic proteins - endogenous

Question 6

MHC II is a source of what type of protein?

Answer 6

Endocytosed protein - exogenous

Question 7

What is MHC I expressed on?

Answer 7

All nucleated cells

Question 8

What is MHC II expressed on?

Answer 8

Professional antigen presenting cells ie APCs - dendritic cells, macrophages, B cells

Question 9

Peptide length of MHCI

Answer 9

8-10 AA

Question 10

Peptide length of MHCII

Answer 10

Over 13 AA

Question 11

Function of MHC I

Answer 11

Amateurs - the alert cytotoxic T cells of infection

Question 12

Function of MHC II

Answer 12

Professionals - coordinate adaptive immune response

Question 13

Professional APCS

Answer 13

Dendritic cells
macrophage
B cells

Question 14

What do professional APCs express?

Answer 14

MHC II constitutively
Can provide co-stimulatory signals for T cell activation

Question 15

Dendritic cell antigen uptake method

Answer 15

Efficient at phagocytosis
Pinocytosis
Receptor mediated endocytosis
Initiates T cells express responses

Question 16

Macrophages antige uptake method

Answer 16

Phagocytosis of microbes and debris
Present antigens to CD4+ T cells
(helper)

Question 17

B cells antigen uptake method

Answer 17

Receptor mediated uptake (BCR-specific)
Highly efficient for specific antigens

Question 18

Cellular process of antigen presentation

Answer 18

Can either be MHCI pathway or MHC II pathway

Question 19

MHC I pathway of antigen presentation

Answer 19

Acquisition
Tagging
Proteolysis
Delivery
MHCI loading
Presentation

Question 20

MHC II pathway of antigen presentation

Answer 20

Acquisition
Tagging and proteolysis
Delivery of peptides
Loading and export
Crosspresentation

Question 21

MHC I presentation used for

Answer 21

Cytosolic
Intercelllar antigens

Question 22

MHC II pathway used for

Answer 22

Endocytosis
Extracellular antigens

Question 23

Acquisition for MHC I pathway

Answer 23

Cytosolic proteins (often viral) targeted for degredation

Question 24

Tagging for MHC I pathway

Answer 24

Proteins tagged with ubiquitin for proteasomal degradation

Question 25

Proteolysis for MHC I pathway

Answer 25

Proteasome cleaves proteins into peptides

Question 26

Delivery for MHC I pathway

Answer 26

TAP1/ TAP 2 transport peptides into ER lumen

Question 27

MHC I loading for MHC I pathway

Answer 27

MHCI alpha chain associates with beta2-microglobin, calnexin, tapasin and Erp57 Peptides loaded onto MHCI in ER

Question 28

Presentation for MHC I pathway

Answer 28

MHC I peptide complex traffics to plasma membrane for recognition by CD8+ T cells ie APCs

Question 29

Acquisition for MHC II pathway

Answer 29

Phagocytosis Pinocytosis Receptor mediated endocytosis

Question 30

Tagging and proteolysis for MHC II pathway

Answer 30

Antigen degraded in endosomoes/ lysosomes by acid proteases Eg Cathepsins

Question 31

Delivery of peptides for MHC II pathway

Answer 31

MHC II associates with invariant chain Traffics to MIIC compartment CLIP occupies peptide binding groove temporarily

Question 32

Loading and export for MHC II pathway

Answer 32

HLA-DM catalyses CLIP removal This allows peptide loading MHC II peptide complex exported to cell surface for recognition by CD4+ T cells

Question 33

Cross presentation for MHC II pathway

Answer 33

Allows exogenous antigens to be psented on MHC I cytosolic antigens can also be presented on MHC II via autophagy

Question 34

Evasion strategies by EBV EBNA1 (virus)

Answer 34

Glycine/ alanine repeats resist proteasomal cleavage

Question 35

Evasion strategies by HCMV V56, HSV ICP47 (virus)

Answer 35

Blocks TAP transporters

Question 36

Evasion strategies by adenovirus E19

Answer 36

Blocks MHC I-tapasin interaction

Question 37

Evasion strategies by MK3(mouse herpes virus)

Answer 37

Ubiquitin ligaments targets MHC I for degredation

Question 38

What molecule are viral evasion strategies targeted at?

Answer 38

MHC I

Question 39

What molecule are bacterial evasion strategies targeted at?

Answer 39

MHC II

Question 40

Evasion strategies by salmonella and mycobacterium tuberculosis (bacteria)

Answer 40

Blocks phagososme-lysosome fusion

Question 41

Evasion strategies by lysteria monocytogenes (Bacteria)

Answer 41

Listerialysin O forms pores to escape phagosome

Question 42

What do tumour cells do to MHCI?

Answer 42

Downregulate it This reduces CD8+ T cell recognition therefore Immune evasion

Question 43

What can mutations do to dendritic cells?

Answer 43

Mutations in antigen processing genes or tumour derived factors eg IL6, IL10 can suppress dendritic cell maturation

Question 44

What can B cell malignancies do?

Answer 44

Disrupt HLA-DM CLIP-loaded MHC II persists This impairs CD4+ T cell activation

Question 45

What are polymorphisms in MHC genes linked to?

Answer 45

Susceptibility to autoimmune diseases Eg HLA-B27 in ankylosing spondylitis