Lecture 31 Flashcards
TCR structure
Composed of an alpha and beta chain
Each has a variable and constant region
Contents of alpha chain of TCR
Multiple V and J segments
Contents of beta chain of TCR
Multiple V, D, and J segments (like heavy chain in BCR)
Where does TCR somatic recombination take place
Thymus, irreversible
Combinatorial diversity of TCR in alpha and beta chain
Alpha chain–> VJ
Beta chain–> VDJ
Combination of alpha and beta chain
Similarities in mechanisms of TCR and BCR recombination
1) V, D, and J segments are flanked by RSS recognized by RAG 1 and 2
2) Artemis cuts DNA hairpins
3) TdT adds non-coded nucleotides in the joining regions
Differences in BCR and TCR recombination
BCR
Ig Heavy chain–> D segment is surrounded by 2 RSS BOTH with 12-bp spacing
TCR
Beta chain–> D segment has a 5’ 12bp RSS and a 3’ 23bp RSS
How many CDRs does TCR have per chain
3 CDRs per chain
Which CDR in TCR is the most important for diversity
CDR3
Where are CDR1 and 2 encoded in TCR
Within V segments of alpha and beta chains
Where is CDR3 encoded in TCR
In the D and J segments
What does Allelic exclusion ensure
That each B cell synthesizes only 1 allele for a heavy chain and 1 allele for a light chain
(through genomic silencing of other chromosomes (methylation))
Consequence of Alternative RNA splicing
1) Expression of IgM vs IgD
2) If immunoglobulin is secreted vs transmembrane
5 Isotypes of Heavy chains BCR
1) M (mu)
2) D (delta)
3) G (gamma)
4) A (alpha)
5) E (epsilon)
Which immunoglobulin classes have variants
IgG and IgA
Where does secondary diversification occur
In Germinal Center after B cell has received signal 1 and 2 AGAIN
Outcome of Somatic hypermutation
Higher affinity for its antigen, specificity remains the same
What is class switching
Process that replaces 1 heavy chain constant region with one of a different isotype
What do somatic hypermutation and class switching mechanisms act on
Already rearranged Ig genes, where V(D)J recombination has occurred in the variable region (can’t go back)
Where does somatic hypermutation take place
On activated B cells in peripheral lymphoid organs (germinal center of lymph nodes)
How does somatic hypermutation improve antigen binding
High rate of point mutations in V gene segments
What is affinity maturation
When point mutation of somatic hypermutation in V gene sequences are selected for increased affinity for antigen
Occurs during primary, secondary, or tertiary responses
What informs class switching
Cytokines secreted by TFH in germinal center
What induces class switching to IgE
IL-4 release from Type 2 response
When does Class switching occur
After B cell activation, irreversible
What guides Class switching
Switch regions located upstream of each C gene
