4. Antibody structure, diversity and antigen recognition Flashcards
in which region of the Ab does it exhibit Ag specificity?
Variable
how many hyper-variable regions in heavy and light chains each?
3
CDR?
complementatory determining regions
what are the CDRs?
1,2 and 3
what do the CDRs make up?
paratope of ab
in what 3 ways are the CDRs complementary to the antigen?
shape
hydrophobiciity
charge
what does an Ig domain consist of?
1 polypeptide chain folded into:
- 2 x anti-parallel beta-pleated sheets
- intra-chain disulphide bond
function of hinge region on Ab?
allows each Ab binding site to act independently
what mechanism allows many Ab to be produced from a small number of genes?
somatic recombination
Describe process of formation of constant region of heavy chain
- DNA - intron, exon, hinge region
- transcription creates RNA
- RNA splicing creates mRNA
- Translation creates constant region of heavy chain
Describe process of formation of variable region of heavy chain
- Germline DNA = V, D, J and constant region with introns in between
- somatic recombination 3 x
a) move DJ together
b) move VDJ together
c) Move VDJ to join constant region - transcription to form RNA
- RNA splicing to form mRNA
- translation to form polypeptide chain
Describe process of formation of variable region of light chain
same as heavy chain V region - no D fragment
how many different types of V regions for heavy chain?
40
how many different types of D regions for heavy chain?
25
how many different types of J regions for heavy chain?
6
What codes for most of the 3rd hypervariable region? why?
V and D regions - there are the most of these
on the DNA - what is the L region?
Leader region - used to target polypeptide into the endoplasmic reticulum during synthesis
What occurs in RNA splicing?
intron/exon RNA sequences are removed
what segment codes for CDR1?
V
what segment codes for CDR2?
V
what segment codes for CDR3?
VDJ - hypervariable
how is variation of Ab added for light variable chains?
2 types of light chain - kappa and lambda
2 types of junctional diversity?
- during recombination - exons remove AA
2. Terminal deoxyribonucleotidyl transferase (TDT) adds random nucleotides to VDJ segments
during class switching, which part of the Ab changes?
constant region
which 2 enzymes are involved in class switching from IgM to IgA?
AID - activation induced deaminase
UDG - uracil -DNA glycosylase
what does AID do?
during somatic recombination - converts cytosine to uracil
what does UDG do?
repairs mismatched bases C-G and U-A
what occurs to Ag-Ab affinity over an immune response?
the affinity increases
how does Ag-Ab affinity increase over time?
somatic hypermutation in variable regions - mutations in the AID and UDG
for Ab with high Ag affinity, do they have a high or low dissociation constant? (Kd)
low
what occurs to affinity when the concentration of Ag decreases?
only mutated B cells which produce high affinity Ab are stimulated
what does isotypic mean?
variations of heavy and light chain in an Ab
what does allotypic mean?
genetic allele differences intraspecies
what does idiotypic mean?
variations of paratopes in Ab
different types of non-covalent forces between Ab and Ag?
- electrostatic
- VDW
- hydrogen bonding
- hydrophobic
what is the valence of an Ab?
number of binding sites for Ag on a Ab
