Antibodies, T cell receptor, MHC ic5 elearning

Question 1

Where does Fc domain of antibody bind to

Answer 1

Fc domain binds to Fc receptor of first line immune cells eg. macrophages, NK cells, neutrophils

Question 2

What does the T cell receptor consist of

Answer 2

alpha chain and beta chain

Question 3

Function of TCR

Answer 3

bind to ligand (antigen presented by MHC) → trigger signal transduction → receptor activation and downstream signalling

Question 4

What does the T cell receptor complex consist of

Answer 4

T cell receptor and CD3 adaptor proteins

Question 5

Function of CD3 adaptor proteins

Answer 5

signal transduction

Question 6

3 types of CD3 dimers

Answer 6

εγ (epsilon gamma)
ες (epsilon sigma)
ζζ (zeta zeta)

Question 7

Does CD3 dimers contribute to the diversity of antigen binding or signal transduction?

Answer 7

No, CD3 proteins are invariant (constant, sequence never changes)

Question 8

How many ITAMs are there in one TCR complex?

Answer 8

10
2 from epsilon sigma, 2 from epsilon gamma, 6 from zeta zeta

Question 9

How does ITAM help in signal transduction?

Answer 9

Upon antigen binding, tyrosine residues on ITAMs get phosphorylated, initiate series of downstream T cell signalling events and T cell activation

Question 10

How does hypervariability occur in CDR of T cells?

Answer 10

Genetic recombination of DNA segments in genes encoding for Va and Vb regions of TCR

Va (Variable region of Alpha chain)
V and J segments → CDR1a, CDR1b, CDR1c

Vb (Variable region of Beta chain)
1) D and J segments
2) (Followed by) V, D, J segments → CDR1b, CDR2b, CDR3b

Question 11

How does hypervariability of T cells benefit T cells?

Answer 11

Hypervariability can allow T cell receptors to recognise and bind to different antigens presented by MHC molecules

Question 12

How does hypervariability of CDR occur in B cells?

Answer 12

B cell receptors = Antibodies stuck on surface of B cell

Progenitor B cells rearrange Ig genes → resulting in different CDR → different clones of immature B cells

Development of naive B cells is INDEPENDENT of antigen stimulation

Question 13

How does gene rearrangement occur in B cells upon antigen stimulation?

Answer 13

B cells mature to plasma cells and produce IgM (pentameric)

Gene rearrangement (occurs twice)
Step 1: Class switching
Gene rearrangement of constant regions (Fc domain) of IgM → IgG

Step 2
Each B cell clone undergoes gene rearrangement to Vl and Vh regions of IgG genes
Each B cell clone will have different hypervariable CDR that will have different antigen specificity
Different mature B cell clones produce different IgG antibodies → contain different CDRs to bind to different epitopes

Question 14

How are MHC molecules displayed for MHC class 2 cell?

Answer 14

Antigen presenting cell (APC) = Phagocytes (Macrophage, Dendritic cells)

1) APC phagocytose pathogen, pathogen broken up into antigenic fragments

2) MHC Class 2 protein binds to antigenic fragment, presents to CD4 T cells in the form of peptide-MHC (pMHC)

Question 15

Which cells have MHC Class 1 vs MHC Class 2

Answer 15

MHC Class 1: Nucleated cells, platelets

MHC Class 2: APC, B cells

Question 16

What kind of fragments bind to MHC Class 1 vs MHC Class 2

Answer 16

MHC Class 1: endogenous antigens eg. self, viral components, neoantigens from cancer cells

MHC Class 2: exogenous antigens from invading pathogens

Question 17

Which T cells bind to MHC Class 1 vs MHC Class 2

Answer 17

MHC Class 1: CD4 T cells
MHC Class 2: CD8 T cells

Question 18

Role of CD8 and CD4 receptor

Answer 18

Bring MHC and TCR closer together, in close proximity for the TCR to bind to the antigen on the MHC

Question 19

How is MHC expression regulated

Answer 19

via cytokines (interferon alpha and interferon gamma)

Question 20

How does variation occur between MHC molecules (2 ways)

Answer 20

1) Polygenic: many different genes produce different MHC Class 1 and 2 molecules → Present all the different available antigens (from invading pathogen) to T cells → Provide broad coverage

2) Polymorphic: each gene has different alleles → Provide broad coverage against different pathogens