L6 - Cellular responses

Question 1

What do TCRs recognise?

Answer 1

Peptide fragments of foreign proteins

Question 2

What do CD4 T cells recognise?

Answer 2

Antigens presented on the surface of professional antigen presenting cells (APCs)

Question 3

What do CD8 T cells recognise?

Answer 3

Antigens presented on the surface of all nucleated cells

Question 4

Describe the structure of a TCR

Answer 4

Made of one alpha chain, one beta chain. Each has a variable region (V), constant region (C), hinge (H), transmembrane region and a cytoplasmic tail. The tails are joined by a disulphide bond.

Question 5

What is the purpose of the positive charge on the membrane spanning region of the TCR?

Answer 5

To balance the negative charges on the CD3 components and zeta chains

Question 6

How many TCRs, CD3 components and zeta chains associate?

Answer 6

2 of each.

Question 7

Which part of the TCR is responsible for the signalling?

Answer 7

The ITAMs (Immuno-receptor Tyrosine-based Activation Motif)

Question 8

What mechanisms generate diversity in TCRs?

Answer 8

Somatic recombination between V, D, J (Beta chain) and V, J (alpha)segments. Also junctional diversity due to imprecise joining and addition of nucleotides by TdT

Question 9

What is the structural difference between MHC class 1 and MHC class 2?

Answer 9

MHC class 1 is made of only an alpha chain, MHC class 2 made of alpha and beta chain

Question 10

What stabilises the MHC class I molecule?

Answer 10

The association of a beta2-microglobulin

Question 11

What is the difference in membrane spanning regions between each MHC class?

Answer 11

MHC I has 1 memb spanning region while MHC 2 has 2 memb spanning regions

Question 12

Which portions of the TCR recognise the peptide presented by MHC

Answer 12

Hypervariable loops / complementarity determining regions (CDRs)

Question 13

Which MHC does the co-receptor CD8 work with and what does it bind to?

Answer 13

CD8 is a co-receptor for the TCR and binds to the alpha3 subunit of the MHC I

Question 14

Which MHC does the co-receptor CD4 work with and what does it bind to?

Answer 14

CD4 is a co-receptor for the TCR and binds to the beta2 subunit of the MHC II

Question 15

Functions of T helper cells (expressing CD4)

Answer 15

Cytokine production, macrophage activation, “help” for B cells, cytotoxic T cell responses

Question 16

Functions of T cytotoxic cells (expressing CD8)

Answer 16

Cytotoxic lysis of infected tumour cells

Question 17

Where do the peptides originate when presented by MHC I

Answer 17

Cytosolic antigens (endogenous pathway)

Question 18

Where does the assembly of peptide-class 1 complexes occur?

Answer 18

In the ER

Question 19

What is the function of calnexin?

Answer 19

Chaperone which binds alpha chains until beta2-microglobulin binds

Question 20

Which cells is the MHC class II pathway limited to

Answer 20

Professional antigen presenting cells

Question 21

In the MHC class II pathway what is the origin of the antigens?

Answer 21

Extracellular or vesicular - exogenous pathway.

Question 22

List the three professional antigen presenting cells

Answer 22

Dendritic cells, macrophages and B cells

Question 23

What is the central chaperone for the class II pathway?

Answer 23

The invariant chain (Ii)

Question 24

What is the role of HLA-DM?

Answer 24

It binds to the MHC II molecule, releasing CLIP (the remnant of the invariant chain, Ii) and allowing other peptides to bind. The MHC II molecule then travels to the cell surface.

Question 25

Name ways that dendritic cells can take up antigens

Answer 25

Macro-pinocytosis, receptor mediated endocytosis, viral infection

Question 26

Which three signals from APCs do naïve T cells receive (in the blood)?

Answer 26

Signal 1 - Activation - TCR and CD4 co-receptor bind to MHC class II 
Signal 2 - Survival - costimulatory molecules B7.1 (CD80) and B7.2(CD86) interact with co-stimulatory receptor CD28 on T cell surface
Signal 3 - Differentiation - variety of cytokines eg IL-1, IL-12

Question 27

What determines the which T cell subset will be produced?

Answer 27

The various cytokines produced by APCs

Question 28

List the fate determining cytokines and state which cell types they determine.

Answer 28

IFN-gamma + IL-12 produce Th1 cells
IL-4 produces Th2 cells
TGF-beta + IL-6 + IL23 produce Th17 cells
IL-6 produces Tfh cells
TGF-beta + IL-2 iTreg cells