Block D - Microbial Growth

Question 1

What is signal transduction, in context to T cell activation (1 mark)

Answer 1

signal transduction refers to the cascade of intracellular biochemical events triggered when a T cell receptor (TCR) binds to an antigen presented on an APC.

Question 2

What co-stimulatory signals are involved during T cell activation by a APC?

Answer 2

CD28 on T cell binds to CD80/CD86 on the APC

Question 3

After the initial trigger of T activation, how are kinases activated by Lck? (2 marks)

Answer 3

-Lck is associated with CD4 or CD8 and becomes activated upon TCR
-Lck phosphorylates Immunoreceptor Tyrosine-Based Activation Motifs (ITAMs) within the CD3 and zeta subunits of the TCR complex

Question 4

After the initial trigger of T activation, how are kinases activated by ZAP-70? (2 marks)

Answer 4

-ZAP-70 is recruited to phosphorylated ITAMs (see Lck question)
-Lck activates ZAP-70, initiating downstream signalling cascades

Question 5

What 3 major pathways does T cell activation activate?

Answer 5

MAPK, PI3K-Akt and NF-κB

Question 6

Why is signal transduction an important process?

Answer 6

it ensures that T cell activation is a highly regulated process.

Question 7

Briefly describe the cytosolic/endogenous pathway?

Answer 7

presents intracellular antigens (viral proteins or proteins from intracellular bacteria) to CD8+ cytotoxic T cells

Question 8

Which MHC class does the cytosolic/ endogenous pathway use?

Answer 8

MHC class I

Question 9

Briefly describe the endocytic/exogenous pathway?

Answer 9

presents extracellular antigens (bacterial toxins, extracellular bacteria) to CD4+ helper T cells

Question 10

Which MHC class does the endocytic/exogenous pathway use?

Answer 10

MHC II

Question 11

Detail the steps in the endogenous/cytosolic pathway (5 marks)

Answer 11

-proteins are degraded into peptides by the proteasome
-immunoproteasomes, induced by interferons, optimise peptide generation for MHC I binding
-peptide transported into ER by TAP (transporter associated with antigen processing?)
-in the ER, peptides bind to MHC class I with the help of chaperones like tapasin and calnexin.
-MHC class I complexes are transported to the cell surface

Question 12

Detail the steps in the exogenous/endocytic pathway (4 marks)

Answer 12

-antigens are internalized by APCs via phagocytosis
-these antigens are degraded into peptides in acidic endosomal and lysosomal compartments
-in the ER, the invariant chain directs MHC II to an endosomal compartment, where it is degraded, leaving a fragment called CLIP
-HLA-DM facilitates the exchange of CLIP for antigenic peptides, allowing peptide loading

Question 13

Name 3 examples of APCs

Answer 13

dendritic cells, B cells, macrophages

Question 14

What processing site does the endogenous/cytolytic pathway use? (2 marks)

Answer 14

cytoplasm and ER

Question 15

What processing site does the exogenous/endolytic pathway use? (2 marks)

Answer 15

endosomes and lysosomes

Question 16

Describe the structure for MHC class I? (4 marks)

Answer 16

-alpha chain is composed of 3 domains (α1, α2, and α3)
-α3 domain is a highly conserved Ig-like domain and interacts with CD8 co-receptors
-the beta 2 microglobulin stabilizes the MHC I molecule
-peptide-binding groove

Question 17

Which segment stabilises the MHC class I molecule

Answer 17

β2-microglobulin

Question 18

In which segment does small peptides bind to the MHC class I molecule

Answer 18

peptide-binding cleft

Question 19

Describe the structure for MHC class II? (4 marks)

Answer 19

-two alpha chains α1 and α2
-two beta chains β1 and β2
-peptide binding groove formed by α1 and β1 domains

Question 20

In MHC II, Peptide-binding cleft is ______, allowing accommodation of _____ peptides.

Answer 20

open-ended, longer

Question 21

IN MHC I, is the end of binding groove open or closed?

Answer 21

closed

Question 22

Describe the structure T cell Receptor. (3 marks)

Answer 22

-heterodimer stucture ( alpha and beta chain)
-each α and β chain has a variable and constant
-antigen-binding site is formed by the combination of the Vα and Vβ regions

Question 23

How does the TCR stay anchored to the membrane? (2 marks)

Answer 23

-α and β chains of the TCR have regions that anchor the receptor in the T-cell membrane.
-the membrane-spanning regions of these chains are hydrophobic, allowing them to embed within the lipid bilayer of the cell membrane

Question 24

What is the antigen binding site of the TCR formed by?

Answer 24

a combination of the Vα and Vβ regions

Question 25

The TCR complex is associated with the ____ signaling complex, which transduces signals to activate the T-cell upon ______

Answer 25

CD3, antigen binding

Question 26

Describe what SH2 binds to in TCR signalling? (3 marks)

Answer 26

-SH2 domains are found in ZAP-70, which is a key player in T cell activation.
-upon TCR engagement, the CD3ζ chains become phosphorylated on tyrosine residues. -ZAP-70 contains SH2 domains that recognize and bind to these phosphotyrosines, helping to recruit ZAP-70 to the receptor complex and initiate downstream signaling.

Question 27

Describe what SH3 binds to in TCR signalling? (3 marks)

Answer 27

-SH3 domains in signaling proteins like Grb2 or SHP-1 (a tyrosine phosphatase) also participate in TCR signaling by binding to proline-rich sequences in target proteins.
-These interactions help in organizing the signaling complexes and regulating the activation of downstream pathways.

Question 28

SH2 domain binds specifically to _________ residues in proteins

Answer 28

phosphotyrosine

Question 29

SH3 domain binds to _________ sequences in proteins

Answer 29

proline-rich

Question 30

Describe the alternative to TCR structure (not α or β chains) and in what cells are these found in? (2 marks)

Answer 30

γ (gamma) chain and δ (delta) chain. These are found in γδ T-cells, which are less common and have different functions compared to the more common αβ T-cells.

Question 31

What is the function of the ζ (zeta) chain? (2 marks)

Answer 31

Its a critical signaling molecule and contains ITAMs, which are phosphorylated upon TCR engagement to initiate downstream signaling.

Question 32

What’s the function of the CD3 complex? (1 mark)

Answer 32

its composed of several proteins that help transmit the signal inside the T cell when the TCR binds to its antigen.

Question 33

What is the CD3 complex composed of? (3 marks)

Answer 33

CD3γ (gamma), CD3δ (delta), CD3ε (epsilon)