Antigen processing/recognition by T lymphocytes

Question 1

B cells can bind to _____, while T cells need to be_____

Answer 1

Native antigens; introduced to antigens thru APCs

Question 2

TCR antigen recognition

Answer 2

Only in the form of peptide bound to an MHC molecule on the surface of APC

Question 3

Antigen processing

Answer 3

Pathogen-derived proteins must be degraded into peptides

Question 4

Peptide:MHC complex

Answer 4

Displayed on APC surfaces, where they can be recognized by T cells

Question 5

Antigen presentation

Answer 5

Binding of peptide:MHC complex and its expression on APC

Question 6

2 classes of MHC

Answer 6

MHC molecules bind a variety of peptides in different intracellular compartments

• CD8 binds alpha-3 domain of MHC class 1
• CD4 binds the beta-2 domain of MHC class 2

Question 7

TCR specifically binds ______

Answer 7

BOTH peptide and MHC molecules

Question 8

Professional antigen-presenting cells

Answer 8

• dendritic cells
• macrphage
• B cell

Question 9

Dendritic cell

Answer 9

• Cell type: viral
• Location in lymph node: T cell area
• Antigen uptake: macropinocytosis/phagocytosis (+++) universal antigen uptake
• MHC expression: low on tissue DCs, high on lymphoid tissue DCs
• Co stimulator delivery: constitutive, nonphagocytic lymphoid DCs (++++)
• Antigen presented: peptides, viral, allergens
• Location: ubiquitous

Question 10

Macrophage

Answer 10

• Cell type: bacterium
• Location in lymph node: ??
• Antigen uptake: phagocytosis (+++)
• MHC expression: inducible by bacteria and cytokines (- to +++)
• Co stimulator delivery: Inducible (- to +++)
• Antigen presented: particulate antigens, intra/extracellular pathogens
• Location: lymphoid tissue, connective tissue, body cavity

Question 11

B cell

Answer 11

• Cell type: microbial toxin
• Location in lymph node: follicle
• Antigen uptake: antigen-specific receptor (++++)
• MHC expression: constitutive, increases on activation (+++ to ++++)
• Co stimulator delivery: inducible (- to +++)
• Antigen presented: soluble antigens, toxins, viruses
• Location: lymphoid tissue, peripheral blood

Question 12

What cell type is the best APC?

Answer 12

Dendritic cells

- are widely distributed in the body, can present any possible antigen derived peptide

Question 13

What makes a cell “professional”?

Answer 13

Able to activate T cells

Question 14

What is the difference between immature and mature cells?

Answer 14

Immature: uptake and process antigens (little MHC class 2)

Mature: present antigen (lots of MHC class 2)

Question 15

How do DC mature?

Answer 15

DC take up bacterial antigens in the skin and then move to enter a draining lymphatic vessel –> DCs bearing antigen enter draining lymph node where they settle in the T cell areas
mature on taking antigen from infected sites to secondary lymphoid organs

Question 16

Where is MHC located in immature T cells?

Answer 16

All MHC class 2 are inside, as MHC moves to the surface the cell matures

Question 17

Classical model

Answer 17

Migration of immature DC from the periphery to the T cell areas of the lymph nodes only occurs in response to microbial stimulation
- pathogen induced migration

Question 18

Revised model

Answer 18

Steady state migration occurs constitutively in the apparent absence of microbial stimulation

• mechanism by which DC can sample and engulf self proteins and food antigens to naive T cells to establish/maintain peripheral tolerance
• pathogen induced migration

Question 19

Direct presentation

Answer 19

Peptides generated in cytosol are transported to ER, where they bind MHC class 1 molecules and presented to CD8+ T cells

Question 20

Direct presentation (CD4)

Answer 20

Peptides generated in acidified intracellular vesicles presented by MHC class 2 molecules to CD4+ T cells

Question 21

Cross presentation

Answer 21

Allows extracellular antigens to be processed and displayed within MHC class 1 molecules to CD8+ T cells (in addition to MHC class 2 and CD4+ T cells)

Question 22

Receptor mediated endocytosis of bacteria

Answer 22

• MHC class 2

- CD4 T cell

Question 23

Marcopinocytosis of bacteria or viruses

Answer 23

• MHC class 2

- CD4 T cell

Question 24

Viral infection

Answer 24

• MHC class 1

- CD8 T cell

Question 25

Cross presentation of exogenous viral antigens

Answer 25

- MHC class 1 | - CD8 T cell

Question 26

Transfer of viral antigens from infected DC to resident DC

Answer 26

- MHC class 1 | - CD8 T cell

Question 27

Questions that only cross presentation can answer

Answer 27

- How to CD8+ T cell responses are primed to infectious organisms that do not infect APCs? - How can DCs prime cytotoxic T cells against pathogens that are restricted to the endocytic pathway and never reach the cytosol? - Pathogen infected DCs are often functionally compromised, how can they present antigens efficiently?

Question 28

Autophagy

Answer 28

Presentation of cellular antigens by MHC class 2 molecules

Question 29

Exceptions to the rules of antigen presentation

Answer 29

- cross presentation | - autophagy

Question 30

Why is yeast used in immunology research?

Answer 30

Can generate multiple clones quickly

Question 31

How does autophagy control innate and adaptive immunity?

Answer 31

- direct pathogen elimination - regulation and effector function of PRRs - regulation of inflammasome activation and alarmin secretion - cytoplasmic Ag processing for MHC 2 presentation and T cell homeostasis

Question 32

Macroautophagy

Answer 32

immunological autophagy

Question 33

How are MHC 1 molecules expressed on APCs

Answer 33

+++ on T cells, B cells, macrophages, DC, and neutrophils + on thymic epithelium, liver hepatocytes, kidney epithelium, and brain

Question 34

How are MHC 2 molecules expressed on APCs

Answer 34

+++ on B cells and DC + on T cells ++ on macrophages +++ on thymic epithelium

Question 35

Erythrocytes

Answer 35

Do not express either MHC 1 or 2

Question 36

Degenerate (promiscuous) binding specificity

Answer 36

MHC molecules have peptide binding sites that are capable of binding peptides of many different amino acid sequences - MHC have germline configuration = less diversity, so they need to be promiscuous

Question 37

Peptide binding groove

Answer 37

Peptide binding site on the surface of the MHC molecule within which a single peptide is held tightly by non covalent bonds

Question 38

What do alpha/beta TCRs recognize?

Answer 38

Peptide presented at cell surfaces by MHC molecules

Question 39

Where do peptides bind to MHC class 1?

Answer 39

Endoplasmic reticulum

Question 40

Where are MHC class 2 peptides generated?

Answer 40

In acidified intracellular vesicles

Question 41

Cross presentation enables ____

Answer 41

Professional APCs to stimulate cytotoxic CD8 T cell responses against viruses that do not infect them directly