TCR Diversity Flashcards
What does each TCR fam have?
Several V gene segments
Several J segments
1 or 2 constant gene segments
What does the Beta gene family also contain?
2-3 Diversity gene segments
How is TCR rearrangement regualted?
In a sequential, stepwise fashion
Which chain rearranges first?
Beta chain
What does the successful rearrangement of TCR B allow?
Allows for the thymocyte to rearrange the alpha chain
What is required to facilitate rearrangement?
RAG 1 and 2
What does RAG stand for?
Recombination activating genes
What two things does RAG do?
Initial RSS recognition
DNA cleavage
What does a deficiency in RAG gene result in?
SCID Severe Combined Immune Deficiency (can’t rearrange)
What does RSS stand for?
Recombination signal sequence
What is each V(D)J gene segment flanked with?
RSS
What is the structure of RSS?
Heptamer, 12/23, nonamer
What is the 12/23 rule?
Rearrangement always occurs b/w RSS w/ a 12/23bp spacer
What is the difference b/w IG and TCR RSS?
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
What creates the bulk of the diversity for TCRs?
Combinatorial mechanisms
How is additional variation created in TCR?
Junctional diversity
What are the 3 principal mechanisms
Junctional Flexibility
P-nucleotide Addition
N-nucleotide Addition
Why do we want to focus the diveristy at the CDR3?
Because it is where it meets the peptide?
What does junctional diversity do?
it adds 0-6 nucleotides at each joint
What does the V gene segment code for? What does it recognize?
It codes for CDR1 and CDR2 which are responsible for MHC recognition
What do the D and J gene segments code for? What is it responsible for?
CDR3 which is responsible for Ag recognition
Why do we have limited V?
So that we can recognize MHC
Why do we have diverse D and J?
So that we can recognize Ag
What is CDR3 coded by?
The V(D)J joint
Where is allelic exlcusion strict and not strict?
Strict in beta not in alpha
What does the successful rearrangement of the TCR Beta chain mean?
It tells the second allele to stop rearrangement (allelic exclusion)
What type of allelic exclusion happens with the alpha chain?
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
Why is allelic exclusion so critical to the Ig genes but not for TCR?
Not sure
What problems can the lack of TCR allelic exclusion cause?
Autoimmunity
How can allelic exclusion lead to autoimmunity?
The 2nd TCR mediates autoimmunity while the 1st TCR mediates + and - selection
