Antigen recognition (8) Flashcards
What complex recognises and aligns the RSSs adjacent to the gene segments to be joined?
RAG1 RAG2 complex.
What three steps occur once RAG1 and RAG2 have recoginsed and aligned RSS sequences?
- Endonuclease activity introduces 2 ssDNA breaks close to RSSs.
- A DNA hairpin is created at the segments to be joined and a flush ds break at the end of the heptamers.
- Blunt ends ligated to form a signal joint. Nicked sequence is repaired to form the coding joint.
How can sequence variability be achieved in the coding joint?
It can be nicked at various points and TdT can add or removed nucleotides.
Where does antigen independent B cell differentiation take place?
Bone marrow.
How many nucleotides can TdT add?
Up to 12. these form the N region.
When does TdT add nucleotides?
During heavy chain rearrangement. This happens in the antigen independent stage in the bone marrow.
What are the three stages of antigen independent B cell differentiation?
- Heavy chain gene rearrangement
- Light chain gene rearrangement
- Selection against self.
When is IgM expressed in B cell differentiation?
After light chain rearrangement in the bone marrow.
What happens in the secondary lymphoid tissue?
Somatic hypermutation- antigen dependant B cell differentiation.
What is expressed in antigen dependant B cell differentiation?
Virgin/ naive B cells express IgM or IgM and IgD.
Where does somatic hypermutation occur, apart from in mature B cells?
Throughout rearranged V regions. In mature B cells it seems to cluster around CDRs.
What is affinity maturation and where does it take place?
The selection of high affinity receptors. It takes place in the 2ndry lymhoid tissue.
What is thought to introduce mutations in somatic hypermutation?
AID- Activation Induced cytidine deaminase.
What happens in class switching?
Same recombined V regions associate with different constant region genes.
What is the purpose of class switching?
To allow for different loclisation or the induction of different effector functions.
What is specifically retained in class switching?
The antigen.
Where does recombination occur in class switching?
Switch regions.
Is class switching reversible or irreversible?
Irreversible.
Why is class switching different to VDJ joining?
Initiated by AID acting at switch regions.
AID allows for class switching and acts at switch regions. What do these regions contain?
G rich tandem repeats.
What does AID do?
Mutates C to U.
Where is AID expressed?
Activated B lymphocytes/
What is AID active on?
ssDNA.
What does AID actively trigger and why is this good?
AID actively triggers DNA repair pathways. These are error prone leading to mutations which introduce additional variation.
What two error prone mechanisms can AID induce?
Mismatch repair
Base excision repair.
What does AID ultimately cause?
Somatic hypermutation.
What do single strand nicks leading to double strand nicks cause?
Class switching.
Is co-expression of IgM and IgD reversible?
Yes.
How can B cells produce different classes of M and D immunoglobulin before class switching has occurred?
Differential transcriptional processing and splicing.
What can differential processing of a primary immunoglobulin transcript control?
Whether the B cells produces membrane bound or secreted IgM.
Does secreted or membrane bound IgM predominated as more B cells become active?
Secreted.
What are the three key features of the A chain locus for TCR genes?
- LVa 70-80 copies.
- Ja - 61 copies
- Ca region
What are the 7 key features of a B chain locus for TCR genes?
- LVb 52 copies
- DB1
3: JB1 6 copies - CB1
- DB2.
- JB2 x 7
- CB2
Is the same recombination machinery used for TCR V region genes as it is for developing B lymphocytes?
Yes.
Do V regions of B or T cell receptors not undergo somatic mutation?
T.
What four features increase the diversity of TCR genes?
- Multiple copies of each V gene segement.
- alpha and beta chain combination.
- Junctional diversity
Where is junctional diversity concentrated in in TCRS?
CDR3 of TCR alpha and TCR beta.
1-5% of T cells are gamma/delta. How are these generated?
Gene rearrangement.
What do gamma/delta TCRS have less of?
V region segments.
What could compensate for gamma/delta TCRS fewer V region segements?
Junctional variability focused at CDR3.
gamma/delta TCR are known to be more ‘antibody like’. What do they appear not to require?
Processing or presentation by MHC.
