29 - B cells: Antibody structure/binding/different classes Flashcards
Structure of immunoglobulin (Ab)
Y shaped glycoprotein
-Contain carbohydrates covalently linked to protein
Immunoglobulin (Ig) the specific chains
protein family to which Ab & BCR belong
-made up of Ig-like domains
-Made up 2 identical disulfide-linked heavy (H) chains + 2 identical light (L) chains
-4 chains in total
Both heavy & light chain have a
a variable region & a constant region
-VL: variable region in light chain
-VH: variable region in heavy chain
-CL: constant region in light chain
-CH: constant regions in heavy chain
Variable regions function
Ag binding
-VL & VH forms Antigen-binding site
–2 identical binding sites per antibody
-Binding result in neutralization & other functions
-It binds to the Ag so that the pathogen can’t bind to its receptor
Constant regions function:
involved in Complement activation
-C1q: classical pathway (can bind to Ag –> cascade)
-Constant region (Fc) can bind to Fc receptors on phagocytes & other cell types
–Mast cells, eosinophils can secrete histamine or granulocytes to kill Ag
if cleaved Antibody: the 3 portions
2 fab fragments + 1 Fc fragment
Fab fragments
2 Fab fragments per antibody
Each has antigen-binding domain & part of the constant H & L chains
Fab = fragment antigen binding
Fc fragment
1 Fc fragment
Constant region of heavy chain
Receptors that bind antibodies recognize the Fc regions (Fc receptor)
Fc = fragment crystallizable
3D structure
2 heavy chains + 2 light chains
Variable & constant regions for each chain
Held together by intra-/interchain disulfide covalent bonds
Both the constant & variable regions are folded in complex 3D structures
Including β strands
what is CDR & where is it
complementarity determining region
Antigen-binding site
-Direct contact with Ag
-Hypervariable loops
-3 loops per variable domain
12 CDR/antibody
-(2x3) x 2
-2 light chains + 2 heavy chains
in Variable Region on (extremities of Ab)
Not part of β strands
CDR has …
greatest variability in the antibody sequence
Antibody binding, what kind of bonding?
Ag binding involves non-covalent bonding between Ig & Ag epitope
o Hydrogen bonds
o Vand er Waals
o Hydrophobic
o Ionic
Antibody: antigen binding (5)
Lock & key specificity
CDR = responsible for this interaction
-At extremities of Ab
Size variability of what’s being recognized by Ab
Variation in Ab itself – CDR varies in length
Location of epitopes can be anywhere on Ag
-BCR recognize Ab in its natural form
5 major classes of Ab
o IgM
o IgD
o IgG
o IgA
o IgE
Key differences between different antibody classes?
Different # of Ig-like domains
Differences in length of constant region of heavy chain
-Differentiated by amino acid sequence of heavy chain (constant region)
–Heavy chain = differentiates different Ab
–Fc fragment of each Ig is different
IgM:
shape
Pentameric
5 IgM linked together via disulphide bonds
IgM: Heavy chain
1 variable region + 4 constant regions
IgM Expressed by
Mature naïve B cells express transmembrane IgM prior to activation
IgM Function
Part of 1st wave of secreted Ab-First one produced after B cell activation
Most effective initiator of complement cascade (C1q)
IgD: heavy chain
1 variable region + 3 constant regions
IgD function:
Part of 1st wave of secreted Ab
IgG heavy chain
1 variable region + 3 constant regions
IgG most abundant in
Most abundant in Plasma (blood)
IgG function
Produced following differentiation in Germinal center
-class switching only happens here
–B cell usually only have IgM/IgD at beginning
Most abundant in serum & strongly induced during an immune response
