TCR Diversity

Question 1

What does each TCR fam have?

Answer 1

Several V gene segments
Several J segments
1 or 2 constant gene segments

Question 2

What does the Beta gene family also contain?

Answer 2

2-3 Diversity gene segments

Question 3

How is TCR rearrangement regualted?

Answer 3

In a sequential, stepwise fashion

Question 4

Which chain rearranges first?

Answer 4

Beta chain

Question 5

What does the successful rearrangement of TCR B allow?

Answer 5

Allows for the thymocyte to rearrange the alpha chain

Question 6

What is required to facilitate rearrangement?

Answer 6

RAG 1 and 2

Question 7

What does RAG stand for?

Answer 7

Recombination activating genes

Question 8

What two things does RAG do?

Answer 8

Initial RSS recognition

DNA cleavage

Question 9

What does a deficiency in RAG gene result in?

Answer 9

SCID Severe Combined Immune Deficiency (can’t rearrange)

Question 10

What does RSS stand for?

Answer 10

Recombination signal sequence

Question 11

What is each V(D)J gene segment flanked with?

Answer 11

RSS

Question 12

What is the structure of RSS?

Answer 12

Heptamer, 12/23, nonamer

Question 13

What is the 12/23 rule?

Answer 13

Rearrangement always occurs b/w RSS w/ a 12/23bp spacer

Question 14

What is the difference b/w IG and TCR RSS?

Answer 14

There is alternative joining of D gene segments in TCR because the RSS flank the regions with one of each. One 12 and one 23 which creates chaos and more ways of joining

Question 15

What creates the bulk of the diversity for TCRs?

Answer 15

Combinatorial mechanisms

Question 16

How is additional variation created in TCR?

Answer 16

Junctional diversity

Question 17

What are the 3 principal mechanisms

Answer 17

Junctional Flexibility
P-nucleotide Addition
N-nucleotide Addition

Question 18

Why do we want to focus the diveristy at the CDR3?

Answer 18

Because it is where it meets the peptide?

Question 19

What does junctional diversity do?

Answer 19

it adds 0-6 nucleotides at each joint

Question 20

What does the V gene segment code for? What does it recognize?

Answer 20

It codes for CDR1 and CDR2 which are responsible for MHC recognition

Question 21

What do the D and J gene segments code for? What is it responsible for?

Answer 21

CDR3 which is responsible for Ag recognition

Question 22

Why do we have limited V?

Answer 22

So that we can recognize MHC

Question 23

Why do we have diverse D and J?

Answer 23

So that we can recognize Ag

Question 24

What is CDR3 coded by?

Answer 24

The V(D)J joint

Question 25

Where is allelic exlcusion strict and not strict?

Answer 25

Strict in beta not in alpha

Question 26

What does the successful rearrangement of the TCR Beta chain mean?

Answer 26

It tells the second allele to stop rearrangement (allelic exclusion)

Question 27

What type of allelic exclusion happens with the alpha chain?

Answer 27

The TCR alpha locus allows 2 chains to rearrange. This means tht 1/3 Tcells will have 2 different alpha chains with one B chain

Question 28

Why is allelic exclusion so critical to the Ig genes but not for TCR?

Answer 28

Not sure

Question 29

What problems can the lack of TCR allelic exclusion cause?

Answer 29

Autoimmunity

Question 30

How can allelic exclusion lead to autoimmunity?

Answer 30

The 2nd TCR mediates autoimmunity while the 1st TCR mediates + and - selection