Chapter 9 - I

Question 1

TCR structure

Answer 1

Structure of TCR complex: TCR, coreceptors (zCD4/8), CD3 signaling protein

alpha/beta TCR: recognizes complex of the MHC and peptide - antigen recognition

CD4/8 co-receptor strengthens the interaction between TCR with the MHC peptide

CD3 and p56Ich - signaling to the nucleus that something is bound

Question 2

T cell Differentiation - I

Answer 2

T cell receptor recognizes a combination of: MHC protein and peptide bound in the cleft of the MHC protein

TH cells recognize peptides presented on MHC class 2 proteins

CTLs recognize antigens presented on MHC class 1 proteins

Question 3

T cell Activation - exogenous antigens

Answer 3

Activating a T cell can be potentially dangerous

To ensure that it is being activated because it really needs to be, T cells requires at least 3 signals to be activated - 2 of these signals come from APCs

Dendritic cells are the most important APC for naive T cells

Signal 1: TCR binding to MHC - foreign peptide complex of the APC (dendritic cell)

Signal 2: CD28 of the T cell binds with B7 of APC, only professional APC can deliver signal 2

Singal 3: Cytokines

Question 4

T cell activation - Signal 1

Answer 4

The TCR complex of the T cell and the MHC peptide complex of the APC

- Need the TCR to bind to the 
  MHC peptide complex that 
  is complementary to the 
  TCR
- Binding of CD4 or CD8 to 
  MHC on APC 
- CD3 signaling complex is 
  activated and delivers 
  signal 1 to nucleus

Question 5

T cell activation - Signal 2

Answer 5

CD28 of the T cell binds to B7 of dendritic cells

T cell is now activated but can;t proliferate yet because it needs cytokine IL-2 for the signal to divide

TH cells can make their owl IL2

CTLs can too but not enough on their own

Question 6

T cell activation - Signal 3

Answer 6

3rd signal for T cell activation and proliferation is cytokines which are made by Tcell itself

T cell needs to get IL-2 to proliferate. TH cells make their own IL-2 and CTLs get extra IL-2 made by Th cells

Question 7

Signal 3 - Autocrine Loop

Answer 7

1. T cells make and secrete IL-2 into extracellular environment
2. IL-2 bind to IL-2 receptor on the cell surface
3. Binding of IL-2 to IL-2
   receptor triggers signaling event –> proliferation and differentiation

Question 8

APCs

Answer 8

Not all APCs are equal

APCs behave differently when in body or in test tube (vivo vs vitro)

Cells in test tubes can be encourages to do things they wouldn’t normally do in the body

eg all cells can be made to phagocytose but this is something most cells don’t naturally do - in test tube we can put in right chemical signals to manipulate them

Question 9

APCs

Answer 9

Dendritic cells: best APC for activation of naive T cell and most important in vivo

Macrophages: 
- In the body, they can 
  present antigen to T cells 
  that have become 
  previously activated
- Also present antigen to 
  become activated 
  themselves
- In vitro, they seem to work 
  to activate naive T cells

B cells:
- In body they present 
 antigen to TH cell in order to 
 receive help (cytokines), B 
 cells do not activate T cells
- B cells are activated by T cells
- In vitro, they seem to work 
  to activate naive T cells

Question 10

Dendritic Cells

Answer 10

Dendritic cells constitutively express MHC 1 and 2 co-stimulatory B7

Dendritic cells can do both endogenous, exogenous, and cross-presentation pathways of presenting and processing antigen

Immature dendritic cells are very phagocytic, they quickly matures and migrate to lymph node to activate naive T cells

Question 11

Antigen presentation

Answer 11

A muscle cell is infected with a virus and presents viral peptides on MHC class 1 (all nucleated cells can do this)
Muscle cells do not express B7 co-stimulatory molecules. What happens to naive CTL that interacts with it

No B7 –> cannot activate CTL that interact with it : signal 1 without signal 2

CTL becomes anergic –> living but non responsive