T cells & the Major Histocompatability Complex (MHC)

Question 1

What are B cells in their native conformation ?

Answer 1

B cell antigens are extracellular in their native

conformation

Question 2

What are T cell antigens ?

Answer 2

T cell antigens are short peptide fragments of processed & presented antigen

Question 3

T cells can only see antigen when it is bound to ?

Answer 3

T cells can only see antigen when it is bound to MHC molecules on the surfaces of antigen presenting cells

Question 4

What are T cell antigens only?

Answer 4

T cell antigen are only protein peptides

Question 5

Both extracellular & intracellular antigen is recognised ?

Answer 5

By T cells

Question 6

Antigen processing in APCs generate ?

Answer 6

Pathogen protein peptides

Question 7

APCs then present peptides bound ?

Answer 7

By Major Histocompatability

Complex (MHC) to T cells – Antigen presentation

Question 8

Explain Cluster of Differentiation 4 (CD4) ?

Answer 8

Identifies one of the main subset of T cells that recognise peptides on MHC class II

Question 9

Explain Cluster of Differentiation 8 (CD8) ?

Answer 9

Identifies one of the main subset of T cells that recognise peptides on MHC class I

Question 10

What does CD8+ Cytotoxic T cells directly do ?

Answer 10

Kills infected/damaged cells (e.g. virus infection or cancer)

Question 11

What does CD4+ T helper cells are ?

Answer 11

Master controllers that function using cytokines to control & regulate other cells

Question 12

What is the subset of CD4+ T helper (Th) cell ?

Answer 12

5 subsets which defend against 
extracellular pathogens (cytokines, macrophage activation)
- Th1 cells
- Th2 cells
- Th17 cells 
- Thfh cells
- Treg cells

Question 13

What is Human Leukocyte Antigens (HLA) ?

Answer 13

• Human leukocyte antigens (HLA) are genes in major histocompatibility complexes (MHC) that help code for proteins that differentiate between self and non-self
• They play a significant role in disease and immune defence
• They are beneficial to the immune system but can also have detrimental effects

Question 14

What is the function of the MHC genes ?

Answer 14

Encode the MHC proteins on
antigen presenting cells that
present antigen

Question 15

Mating with mice that had different MHC genes,

produced ?

Answer 15

Offspring with stronger immune systems able to combat wider variety of diseases

Question 16

MHC class I & class II on antigen presenting cells present peptide antigens to?

Answer 16

CD4 & CD8 T cells respectively

Question 17

What does MHC Class I bind to ? and found on ?

Answer 17

• MHC Class I Binds CD8+ T cells

- Found on all cells

Question 18

What does MHC Class II bind to ? and found on ?

Answer 18

• MHC Class II Binds
  CD4+ T cells
• Found on immune APCs

Question 19

Briefly explain the structure of the MHC ?

Answer 19

• α chain and β chain (in both MHC class II)
• Heavy chain, α chain only and β2- Microglobulin (MHC class I)
• Both consist of non-
  covalent complex of two
  polypeptide chains
• Both have similar folding structure

Question 20

Allelic MHC are inherited in linked groups called ?

Answer 20

Haplotypes

Question 21

Who inherits haplotypes?

Answer 21

Each individual inherits one haplotype from each parent

Question 22

How are MHC alleles expressed ?

Answer 22

• MHC alleles are codominantly expressed: both maternal & paternal MHC genes expressed in offspring
• This gives the best chance for an organism to have SOME capability of presenting all the possible antigen peptides it encounters

Question 23

Nonmatching MHC patterns will result in ?

Answer 23

Rejection of transplanted tissues

Question 24

MHC polymorphism tends to be clustered within groove sites of?

Answer 24

Peptide binding

Question 25

So what do the MHC polymorphism affect ?

Answer 25

This affects the binding of peptide groove: This determines which antigens can be presentation to T cells

Question 26

What are the protein products of MHC genes called ?

Answer 26

Isotypes

Question 27

Why is it that MHC class I the amino acid length is limited ?

Answer 27

MHC class I: Peptide ends buried within molecule limiting length to 8-10 amino acids

Question 28

Is the amino acid length for MHC class II also limited?

Answer 28

``` No. The structure of MHC class II is more open so peptides extend beyond peptide binding groove - Longer & more variable length (13-25aa) than MHC class I ```

Question 29

What is MHC Class I expressed by ?

Answer 29

Expressed by ALL cells (except erythrocytes & neurones)

Question 30

What is MHC Class II expressed by ?

Answer 30

Expressed by professional antigen presenting cells (Dendritic cells, macrophages, B cells)

Question 31

What specific domain of MHC class I does CD8 bind to ?

Answer 31

CD8 binds to α3 domain of MHC class I

Question 32

What specific domain of MHC class II does CD4 bind to ?

Answer 32

CD4 binds the β2 domain of MHC class II

Question 33

What do Cytotoxic T cells have ?

Answer 33

A CD8 co-receptor which cooperates with TCR to recognise peptide on MHC I

Question 34

What do T helper cells have?

Answer 34

T helper cells have a CD4 co-receptor that cooperates with TCR to recognise peptide on MHC II

Question 35

What happens when a CD8+ Cytotoxic T cell sees antigen on MHC I on potentially any nucleated cell (doesn't have to be an immune cells) ?

Answer 35

TCR cell signalling & gene expression: - Activation - Proliferation & differentiation into Cytotoxic effector cells that can lyse infected cells - Produce effector cytokines

Question 36

What happens when a CD4+ Thelper cell sees antigen on MHC II on a professional antigen presenting cell ?

Answer 36

TCR cell signalling & gene expression: - Activation - Proliferation - Differentiation into T helper effector cell subsets (Th1, Th2, Th17...) and ‘help’ activate other cells - Cytokine production