Lecture #5 Flashcards
The structures of BCR and TCR
Structural differences between secreted Ig and BCR
Isotype of an Ab
Different glycosylation pattern on the constant region of the heavy chain
miu, gamma, alpha, epsilon, delta
Allotype of an Ab
WIthin classes (isotypes) one SNP in the gene coding for the isotype is creating more variants
Ex: IgG1,2,3,4
Idiotype of an Ab
Changes in the variable region
Binding sites on immunoglobulins
Groove between CH1 and VH for the binding of C3b C4b
CH2 binding site for the head of C1q
Fc region for FcR
CDR
Complement determining regions on Abs or TCRs
Composed of 3 N’ terminal loops in the variable region which are highly variable and can bind non covalently to the Ag
Also called HV1, HV2, HV3
CDR in TCR
HV1 and HV2 bind specific AA on the MHC
HV3 binds specific AA on the Ag
Genetic modifications in order to increase the pool of possible BCRs and TCRs
- Somatic gene rearrangment
- Junctional diversity
Ig heavy chain genes are found on chr ____ lambda light chain on chr_____ and kappa on chr_____
14
22
2
What is the constitution of the gene goding for Ig heavy chain (general)
Somatic gene rearrangment
Also called VDJ recombination
In the bone marrow, CLP is matured to B cell and in , the process of BCR synthesis, one gene is chosen from each V, D and J genes consisting the variable region
The light chains undergo the same recombination only with V and J
Same happens for TCR in the thymus during T cell maturation
(beta chain has VDJ alpha chain has VJ)
Junctional diversity
Mediated by RAG1/2 recombinases
Only expressed in developing lymphocytes
RAG complex recognize RSS recombination signal sequences at the junctions between VDJ genes
- Binding to RSS
- Hair pin formation and cleavage by artemis endonuclease
- Addition of random nucleotides and ligation
The principle of allelic exclusion
During B cell maturation only one gene for BCR is expressed, either maternal or paternal the other one is inhibited
Junctional diversity defect
Ommen’s syndrome
Partial activity of RAG1/2/Artemis
There will be no B cells and low amount of T cells