B2 antibody structure Flashcards
name the 5 immunoglobin subtypes and describe structure
IgA, IgG, IgM, IgE, IgD
all have 2 Light chains have domains and 4 heavy chains for (IgG, IgA and IgD) and five heavy chains for (IgM and IgE) domains
Describe how the IgG antibody cleaved?
By proteolytic cleavage via papain
explain purpose of 1. Fab regions 2. Fc regions 3. hinge regions
2 fab fragments (contain variable regions & bind antigen)
1 Fc fragment (interacts w/ effector molecules/cells)
Hinge - joins antibody arms
What types of carbohydrates may be found & what does addition of carbohydrates affect
May be N- or O- linked
addition of carbohydrate affects antibody: secretion, solubility & catabolic rate.
- explain HV (CDRs)
2. what are the regions between CRDs called
- hypervariable region/ complementary determining regions: CDR1, CDR2 & CDR3
- determine the antigen specificity to make contact with ligand - FR (framework regions)
- provide a protein scaffold for HV regions
define paratope & epitope
- Paratope: CDRs which make up the antibody combining site.
2. Epitope: antigen combining site (complementary to the paratope)
Describe the antibody domain
‘barrel’ structures: antiparallel beta strands, pack together to form beta sheets (held together by disulphide bonds).
In the folded structure of the light chain V domain HV loops form antigen-binding regions
In a complete antibody molecule pairing of heavy chain + light chain bring together HV loops from each chain to create a single HV surface: forms antigen-binding site.
(as complementary to antigen surface, the HV regions are known as complementarity-determining regions (CDRs). C, carboxy terminus; N, amino terminus.
what type of bonds present between antigen & antibody?
only NON-covalent interactions (weak)
e.g. Van der Waals
what was proved to show antibody diversity
evidence proved that separate genes encode the V and C regions of antibodies & that genes are rearranged in the course of B cell development
describe Light-chain V-region genes
constructed from 2 segments: variable (V) + joining (J). join to form light-chain V-region exon.
V segment is preceded by exon encoding: leader peptide (L) (directs the protein into the cell’s secretory pathways and is then cleaved)
The C region is encoded in a separate exon and is joined to the V-region exon by splicing of the light-chain RNA to remove the L-to-V and the J-to-C introns.
Heavy-chain V regions
Heavy-chain V regions - 3 gene segments
(D) diversity & J -> V joins combined DJ =complete VH exon
The C-region exons + leader sequence, are spliced to the V-domain sequence during processing of the heavy-chain RNA transcript.
L removed after translation, and the disulfide bonds that link the polypeptide chains form
what is the name given to the conserved noncoding sequences
and what is it composed of
recombination signal sequences (RSS)
heptamer (CACATG) & nonamer (ACAAAAACC) seperated by either 12bp or 23 bp of nucleotides.
(*joining gene segments almost always involves 12/23bp rule)
define V(D)J recombinase
complex of enzymes that carry out somatic V(D)J recombination.
(recombination activating genes) RAG-1 & RAG-2 (form a dimer) & develop lymphocyte when recombination occurs.
explain the process of antibody gene rearrangements???
recombination signal sequence -
RSS brought together > RAG complex generates DNA hairpin at coding ends > Artemis: DNA-PK complex opens DNA hairpins, generating palindromic P nucleotides > N-nucleotides additions TdT > Pairing of strands > Unpaired nucleotides are removed by an exonuclease > The gaps are filled by DNA synthesis & ligation to form coding joint.
Name Sources of variation in CDRs of antibodies
CDR1: somatic hypermutation
CDR2: somatic hypermutation
CDR3: (VDJ or VJ junction) gene segment recombination, P-nucleotide addition, N-nucleotide addition**, somatic hypermutation*
