Lymphocyte Receptor Genetics

Question 1

In order for the immune system to recognize a vast array of rapidly evolving microorganisms to provide protection, they must?

Answer 1

1. Generate a diverse repertoire of receptor molecules capable of recognizing microbial pathogens
2. Minimizing the expression of receptors that recognize self-antigens (no self-harming receptors)

Question 2

Immune responses rely on recognition molecules

Answer 2

1. Germ-line encoded PRR

2. Randomly generated (BCRs and TCRs)

Question 3

PRRs

Answer 3

• Germ-line encoded
• Bind to pathogen-associated molecular patterns
• generic molecules found on many different types of pathogens
• Many invertebrates have these same PRRs

Question 4

BCRs and TCRs

Answer 4

• Randomly generated
• Bind to very specific antigens, rather than generic molecules found on many pathogens
• BCRS: structural or soluble antigen
• TCRS: antigen that has been degraded and put on an MHC molecule

Question 5

B-cell receptor

Answer 5

• present exclusively on B lymphocytes

- Contains an antibody of defined specificity

Question 6

T-cell receptor

Answer 6

• present on t lymphocytes

- specific for peptides derived from APC-degraded antigen presented on MHC molecules

Question 7

When BCR or TCR bind to their corresponding antigens

Answer 7

B and T lymphocytes proliferate and differentiate into effector cells that eliminate the microbial threat

Question 8

Immunoglobulin gene segments

Answer 8

V- variable
D- Diversity
J- Joining
C- constant

Question 9

Where does recombination happen?

Answer 9

thymus or bone marrow

Question 10

Where does recombination occur?

Answer 10

• somatic cells

- randomly generate T and B cells

Question 11

Variable region

Answer 11

• interacting with antigen

- creating diversity

Question 12

Light chain

Answer 12

encoded by the V, J, and C gene segments

Question 13

Heavy chain

Answer 13

encoded by the V, D, J, and C gene segments

Question 14

How does the immune system generate a diverse repertoire of receptor molecules capable of recognizing microbial pathogens

Answer 14

Partially by the ability of developing B cells to recombine the V,D, and J gene segments

Question 15

Proteins involved in V(D)J recombination

Answer 15

• RAG1/2
• TdT
• Artemis
• ATM

Question 16

RAG 1/2

Answer 16

• Responsible for recognizing and cutting DNA at the immunoglobulin-encoding region and the RSS
• Recognizes RSS

Question 17

TdT (Terminal deoxyribonucleotidyl transferase)

Answer 17

• Adds non-templated nucleotides to the coding joint

- only in the heavy chain

Question 18

Artemis

Answer 18

Cuts hairpin loops on DNA

Question 19

ATM (ataxia telangiectasia mutate)

Answer 19

Used in cell-cycle, blocks cell cycle until DNA is all repaired

Question 20

How are the different V, D, J, and C gene sequences selected for recombination?

Answer 20

• Recombination is directed by signal sequences
• Each gene is flanked by recombination signal sequences (RSSs)
• One RSS with a 12bp spacer sequence and other RSS with a 23bp sequence are randomly selected

Question 21

RSS

Answer 21

• Has a nonamer and heptameter

- 12 or 23 bp spacer

Question 22

After selection what recombines the different V,D,J, and C gene sequences?

Answer 22

Gene segments are joined by the RAG 1/2 recombinase

Question 23

12/23 rule

Answer 23

One RSS with a 12bp spacer sequence and other RSS with a 23bp sequence are randomly selected

Question 24

V(D)J recombination

Answer 24

1. RAG proteins bind to RSSs and cleaves the DNA
2. Other proteins process the hairpin loops that form after RAG reacts
3. Products include a recombined coding joint and a leftover signal joint that is later degraded
   - Can occur in any direction as long as the correct RSSs are lined up

Question 25

Hairpin loop

Answer 25

- cut by artemis - Can cut in three ways - 5' overhang - blunt end - 3' overhang - Creates cites for P nucleotide addition

Question 26

What are the various mechanisms that generate antibody diversity in naive B cells?

Answer 26

1. Multiple gene segments (which segments are put together) 2. Combinational diversity (between light and heavy chain) 3. P-nucleotide addition (templated nucleotide addition between joints, resulting from asymmetrical cleaving of hairpin structures) 4. Exonuclease trimming (sometimes occurs at junctions, losing and changing reading frames) 5. Nontemplated (N) nucleotide addition (mediated by TdT activity, adding in random nucleotides between joints)

Question 27

Mature B cells express what antibodies

Answer 27

- express both IgM and IgD

Question 28

mRNA splicing

Answer 28

- determines whether the BCR is IgM or IgD | - control whether the cell produces membrane-bound or secreted IgM

Question 29

TCR proteins consist of

Answer 29

- 2 subunits | - alpha and beta

Question 30

Ig heavy chain

Answer 30

- V(D)J recombination - 12/23 rule obeyed - N- nucleotide addition - more than one C region

Question 31

Ig light chain

Answer 31

- V-J recombination - 12/23 rule obeyed - N- nucleotide addition - one C region

Question 32

TCRalpha

Answer 32

- V-J recombination - 12/23 rule obeyed - N- nucleotide addition - one C region

Question 33

TCRbeta

Answer 33

- V(D)J recombination - 12/23 rule obeyed - N- nucleotide addition - one C region