(L23) Adaptive Antigen Recognition in the Immune System

Question 1

What are the components of the BCR complex?
What is responsible for Ag binding and what is responsible for signal transduction?

L23 S8

Answer 1

Membrane bound IgM or IgD:

• Ag binding
• nonsignal transducing (no ITAMs)

Igα and Igβ:

• signal transducing (ITAMs)
• non-Ag binding

Question 2

What are the components of the TCR complex?
What is responsible for Ag binding and what is responsible for signal transduction?

L23 S9

Answer 2

TCR:

• Ag binding
• nonsignal transducing (no ITAMs)

CD3:

• two complexes (εγ and εδ)
• signal transducing (ITAMs)

ζ dimer:
-signal transducing (ITAMs)

Question 3

Describe the state of the BCR/TCR at the stages of pro-lymphocyte, pre-lymphocyte, and immature lymphocytes.
L23 S10

Answer 3

Pro-lymphocyte:
-no receptor

Pre-lymphocyte:
-BCR heavy chain or TCR β chain present with surrogate light or α chain

Immature lymphocyte:
-complete BCR and TCR

Question 4

What are the mechanisms of lymphocyte receptor diversity?

L23 S14

Answer 4

Combinatorial diversification:

• multiple different copies of gene
• V(D)J somatic recombination

Junctional diversity:
-addition of P and N nucleotides at junctions between V, D, and J segments

Somatic hypermutation:
-induced point mutations in V(D)J regions (only in B cells)

Question 5

What enzyme is responsible for V(D)J recombination?

L23 S22

Answer 5

RAG-1 and RAG-2

Only present in lymphocytes

Enzymes select V/D/J copies that will be used, excise DNA of copies that were not selected, and joins ligates DNA so selected copies are adjacent.

Question 6

How are BCR heavy chains and TCR β chains rearranged?

L23 S20

Answer 6

D and J segments are selected and rearranged first

V and DJ segments are selected and rearranged second

Question 7

How are BCR light chains and TCR α chains rearranged?

L23 S27

Answer 7

Light chains and alpha chains do not have diversity (D) segments

Only VJ selection and rearrangement occurs

Question 8

How is junctional diversity created?

L23 S24-25

Answer 8

Recombination cleaves hairpins asymmetrically leaving some overhanging nucleotides.

Terminal doxyribonucleotidyl transferase (TdT) uses overhanging nucleotides as template to created palindromic (P) nucleotides.

TdT then randomly generates N nucleotides to fill gap between strands

Question 9

How are Cμ or Cδ selected to make both μ chains and δ chains for BCRs?

L23 S40

Answer 9

Pre-mRNA which contains VDJ segment and non-adjacent copies of both Cμ and Cδ.

Either the Cμ or Cδ is selected and placed adjacent to the VDJ segment resulting in mRNA for a μ chain or a δ chain

Question 10

How are B cells developed and selected?

L23 S41

Answer 10

Heavy chain is produced first and presented with surrogate light chain. If this fails, cell death occurs.

Cells that successfully produced a heavy chain then produce a κ light chain. If this fails, cell death occurs.

Cells that successfully produce both heavy and light chains are then tested for auto-reactivity.

Nonself reactive B cells are positively selected while self-reactive B cells are negatively selected and undergo BCR editing

Question 11

What is BCR editing?
Why and how does it occur?

L23 S42

Answer 11

B cells that are self reactive cannot be allow to survive.

Initially the BCR was created using the κ light chain (there are two light chain loci κ and λ)

If BCR with the κ chain is self reactive, that chain is disposed of and recombination reoccur using the λ chains this time.

New BCR with λ light chain is tested again. If still self-reactive, cell death occurs.

Question 12

How are T cells developed and selected?

L23 S41

Answer 12

β chain is produced first and presented with surrogate α chain. If this fails, cell death occurs.

Cells that successfully produced a β chain then produce a α chain. If this fails, cell death occurs.

Cells that successfully produce both β and α chains are then tested for auto-reactivity.

Nonself reactive T cells are positively selected while self-reactive T cells are negatively selected undergo cell death

Question 13

What stages of CD4, CD8, CD3 expression do T cells go through and where are they located?

L23 S55-56

Answer 13

CD3-, CD4-, CD8- (pro-T cell):
-occurs from bone marrow to subcapsular zone

CD3+, CD4+, CD8+ (double positive immature T cell w/ TCR):
-occurs in cortex

CD3+, CD4+, CD8- or CD3+, CD4-, CD8+ (single positive w/ TCR):
-occurs in the medulla and in circulation