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Lecture 15 Antigen-Receptor Diversity Part II
Antigen-Receptor Diversity Part II
45
Immunology
Undergraduate 4
04/06/2015

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Term
Gene rearrangement in what region of TCRs is responsible for mammals' ability to produce such a huge variety of B & T cell receptors?
Definition
the variable region
Term
What are the immunoglobulin (BCR) gene clusters found in mammals, and what chain does each code for?
Definition
IGK cluster codes κ light chain
IGL cluster codes λ light chain
IGH cluster codes the heavy chain
Term
How many C genes code the C-region (constant region) of light chains?
Definition
1
Term
How many C genes code the immnoglobulin isotype of heavy chains?
Definition
multiple C genes
Term
True or False

V, D and G genes code the V-region (variable region) of light chains
Definition
False, only V & J
Term
When & where do developing B-cells undergo gene rearrangements to increase receptor diversity?
Definition
early in development in primary lymphoid tissues
Term
What recombinases 'loop out' unneeded DNA from V region genes?
Definition
RAG 1 & 2
Term
True or False

RAG 1 & 2 genes have been conserved throughout evolution
Definition
True
Term
What are the steps of heavy chain recombination? (5)
Definition
1. Random D-J joining
2. Random V-DJ joining
3. Transcription
4. VDJ joining to C gene
5. Translation
Term
What is allelic exclusion?
Definition
silencing of one copy of a heavy chain gene so that only one undergoes recombination
Term
What occurs first, recombination of heavy chains or light chains?
Definition
heavy
Term
What are the steps of light chain recombination? (4)
Definition
1. Random V-J joining
2. Transcription
3. VJ joining to C gene
4. Translation
Term
What light chain rearrangement is attempted first, κ or λ?
Definition
κ
Term
What happens if the first κ light chain recombination is not successful?
Definition
Will first attempt with the other copy of κ, and then with the λ gene if necessary
Term
What happens if none of the light chain recombinations are successful?
Definition
B cell undergoes apoptosis
Term
____ preferentially use λ light chains while _____ preferentially use κ light chains
Definition
Cows
Pigs
Term
What enzymes carry out base deletions during BCR recombination?
Definition
endonucleases
Term
What enzyme can insert N-nucleotides or P-nucleotides into the splice site during BCR recombination?
Definition
deoxynucleotidyl-transferase (TdT)
Term
True or False

B-cells can continue to undergo rearrangements of V-genes even after being exposed to antigens
Definition
True, in the GC
Term
What regions of the binding site on BCRs are able to increase their binding affinity over time? What enzyme causes these random mutations?
Definition
CRD1 and CRD2

cytidine deaminase
Term
During somatic mutations, cytidine deaminase converts ____ to ____. As a result, ______ recognizes these bases as errors or replaces them with ____
Definition
cytosines to uracil
DNA polymerase
thymine
Term
Why does IgM binding affinity never increase over time?
Definition
random somatic mutations doesn't occur until after class switching from IgM to IgG/IgA/IgE
Term
Species with very few V genes are able to increase Ig receptor diversity through....
Definition
gene conversion
Term
During gene conversion, ______ converts cytosines to _____ which are replaced by _______ from pseudogenes
Definition
cytidine deaminase
uracil
nucleotide insertions
Term
How do cattle create diversity in their light chains?
Definition
gene recombination
Term
How do cattle create diversity in their heavy chains?
Definition
gene conversion
Term
True or False

Chickens have a large number of functional V genes
Definition
false
Term
How do chickens create immunoglobulin diversity?
Definition
gene conversion, some somatic mutation
Term
True or False

Truncated avian IgY has a high affinity for binding to Fc receptors
Definition
false
Term
Avian IgY has ____ heavy and ___ light chains and is lacking a ___
Definition
2
2
hinge region
Term
True or False

Fish do not have deoxynucleotidyl transferase and as such are not able to carry out nucleotide insertions during recombination
Definition
false
Term
True or False

Fish have a poor secondary immune response
Definition
true
Term
How do cartilaginous fish BCR/TCR genes differ from mammals & bony fish?
Definition
VDJC fences are arranged in that order in a repeating pattern
Term
True or False

Cartilaginous fish have Ig light chains, but these do not appear to be homologues to the human versions
Definition
true
Term
What are the TCR gene clusters found in mammals, and what chain does each code for?
Definition
TRB contains VDJC genes for beta chain

TRA/D contains VJC genes for alpha chain, and VDJC for δ chain

TRG cluster contains VJC genes for γ chain
Term
How is TCR diversity generated?
Definition
gene recombination
combinatorial association
Term
What is combinatorial association?
Definition
combination of different α and β
chains, and γ and δ chains

OR between different Ig heavy & light chains
Term
What TCR gene cluster undergoes rearrangement first, and where does this occur?
Definition
TRG in the thymus
Term
What happens if TRG rearrangement is unsuccessful in creating a functional γδ TCR?
Definition
TRB & TRA rearrangement will be attempted

-if successful, TRD cluster is deleted
Term
Mice and humans have a ___ combinational repertoire in the TRD and TRG clusters
Definition
diverse/large/varying
Term
Which is more diverse in TRD & TRG clusters, ruminants or mice?
Definition
ruminants
Term
Ruminants are able to carry out combinatorial association between single ____ chain and several ____ chains
Definition

Term
How many IGHJ germline genes to pigs have?
Definition
1
Term
What is the first stage of developing antigen receptor diversity in piglets?
Definition
Recombination of VDJ genes, migration of B cells to GALT & subsequent proliferation
Term
Where does the second stage of developing antigen receptor diversity in piglets occur?
Definition
in intestinal lymphoid organs which are in direct contact with intestinal microflora
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