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26 Cards in this Set

  • Front
  • Back
What did Tonegawa conclude about 'Jumping Genes'?
As the B cell matures, rearrangements in DNA of heavy and light chains occur --> different gene segments brought together to code for entire V region, intervening sequences removed
How does the immune system make a wide range of proteins from single segments of DNA?

What about this process is completely unique to the immune system?
By making different arrangements of V-, J-, and D-regions

Rearrangement leads to PERMANENT loss of intervening chromosomal material
What do RAG-1 and RAG-2 do?
Recombinases that help rearrange DNA to bring V, D, and J segments together
What encodes the V regions of the heavy chain?
3 gene segments:

V (variable)
D (diversity)
J (joining)
What is the order of recombination in encoding for the V region of the heavy chain?
D first recombines with J, then V combines with DJ
On what chromosome is the Human H chain locus?
Chromosome 14
What regions are responsible for encoding the light chain?
V and J
What are two types of L chains?
V kappa, V lambda
On which chromosome is the kappa chain locus?
Chromosome 2
On which chromosome is the lambda chain locus?
Chromosome 22
In what order are the H chains and L chains made via gene rearrangement?

On what type of cells does this process only occur?
H chain first
L chains next: kappa, then lambda

Only occurs on B cells, angtigen-independent
What are the steps for production of a heavy chain?

Where do these events occur?
Nucleus:

Germline DNA --> somatic recombination --> DJ together --> somatic recombination --> VDJ --> transcription --> RNA

Cytoplasm:
RNA splicing --> mRNA --> translation --> polypeptide chain
What are the steps for production of a light chain?
Nucleus

Germline DNA --> somatic recombination --> VJ joined --> transcription --> RNA

Cytoplasm:
RNA --> splicing --> mRNA --> translation --> polypeptide chain
What are heptamer/nonamer recognition sequences?

How are they removed?
23 or 12 base pair separations between V, D, and J regions

Removed when RAG recombination proteins bind, create double stranded DNA breaks--> gaps filled in by DNA polymerase
What is allelic exclusion?

What does this create?
Each cell selects only ONE parental Vheavy and one parental Vlight (kappa or lambda)

Each B cell clone has one BCR
What is the process of allelic exclusion of heavy chains?
Rearrangement starts on both alleles

When one rearrangement is successful, other allele is silenced --> stimulates kappa gene rearrangement

If neither allele successful, cell death
What is the process of allelic exclusion in light chains?
Kappa chain rearrangement first; if successful, silences other allele, starts lambda allele
What is combinational diversity?
Different V, D, and Js
What is junctional diversity?
Random removal/insertion of nucleotides between V, D, and J
What is somatic hypermutation?
When IgM and IgD are expressed on B cells, Tcell-Bcell interaction activates neurotransmitter sequence changes in the VDJ area
What is clonality?
Net outcome of allelic exclusion = single B cell Ig has 2 identical H chains, 2 identical L chains, and one specificity determined by the shape/size of the VH/VL binding groove
What are 6 factors that contribute to the generation of diversity?
1. Multiple V, D, and J segments to choose from
2. Combinatorial diversity - V, D, and J order
3. Junctional diversity - imprecise joining of V, D, and J
4. N-region diversity - insertion/deletion of extra nucleotides
(exonucleotides remove nucleotides, TdT adds)
5. Random assortment of heavy chain with 2 light chains
6. Receptor editing
What are the two types of TCR?

What kinds of gene segments make them up?
alpha-beta
delta-gamma

alpha and gamma determined by VJ
beta and delta determined by VDJ
What are the chromosomal locations of the following human TCR genes?
a. TCR beta
b. TCR alpha and delta
c. TCR gamma
a. chrom. 7
b. chrom 14
c. chrom 7
What are 5 factors that promote TCR diversity?
a. Multiple V, D, and J segments
b. Junctional diversity
c. combinatorial diversity
d. N-region diversity
e. alpha chain is not allelicaly excluded (some T cells have 2 receptors)
What are 2 differences between ab and dg TCRs?
1. gd-TCRs have fewer V, D, J segments --> less diversity; also less junctional diversity

2. ab-TCRs can be biclonal (2 alphas) or monoclonal

gd-TCRs are allelically excluded, always monoclonal