The Prototype Immunoglobulin Molecule

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Lecture 2
Antigens, Receptors and
Immunoglobulins
Antigenic Determinants (Epitopes)
What is an antibody?
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Product of adaptive immunity
Made specifically to bind a unique antigenic
epitope (also called an antigenic determinant)
Possesses an antigen binding site
A product of the Plasma cell
Members of the class of proteins called
immunoglobulins
Receptor-Epitope Interactions and Affinity
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Most biological systems can be viewed in terms of
interactions between receptors and epitopes (“hand
and glove”).
Specificity of the interaction between the receptor and
epitope is determined by the amino acid sequence of
the receptor (“tailoring the glove”).
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If the glove is too big, the glove falls off.
If the glove is too small, you can’t get your hand into it.
If the glove is missing fingers…
Binding of the epitope in the
antigen binding site
GOOD FIT
POOR FIT
antibody combining site
antigen determinant
high attraction
low repulsion
high repulsion
low attraction
Basic Immunoglobulin Structure
The Prototype Immunoglobulin
Molecule
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Fab
VH
VL
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CH1
CL
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CH2
Fc
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CH3
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Heavy Chains (five
types: 
Light Chains (two
types: and
Fab fragment
Fc fragment
Constant and
variable regions
Carbohydrate
Disulfide linkages
Immunoglobulin G (IgG)
Fab
VH
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VL
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CH1
CL
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CH2
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Fc
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CH3
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2 Heavy and 2 Light chains
2 Fab and 1 Fc fragment
4 Subclasses (IgG1, IgG2, IgG3,
IgG4)
Mol. Wt. 150,000
~70-75% of serum
immunoglobulin.
The major antibody of the
secondary immune response
Change in affinity with time
Immunoglobulin M (IgM)
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J-Chain
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10 Heavy and 10 Light chains
10 Fab and 5 Fc fragments
Mol. Wt. ~900,000
<10% of serum
immunoglobulin.
Single J Chain (15 kDA)
The predominant "early"
antibody
Most primitive immunoglobulin
No change in affinity with time
Immunoglobulin A (IgA)
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Monomeric- Serum IgA
~15-20% of serum
immunoglobulins
2 Heavy and 2 Light
2 Subclasses (IgA1
and IgA2)
Found in serum
Secretory Immunoglobulin A (sIgA)
J-Chain
Secretory Component
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4 heavy chains and 4 light chains (dimeric)
J-Chain and secretory component
The major immunoglobulin of secretions
Not found in serum
Immunoglobulin E (IgE)
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CH4
2 Heavy and 2 Light chains
Mol. Wt. ~190,000
Trace serum protein
Note CH4 region on H chain
Associated with atopic or
anaphylactic
hypersensitivity
May play role in immunity
to helminthic parasites
Immunoglobulin D (IgD)
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2 heavy and 2 light chains
<1% of serum
immunoglobulins
Serves as a membrane
receptor on B lymphocytes
May play role in antigenstimulated lymphocyte
differentiation
Take Home Lessons
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What is the basic immunoglobulin structure?
What are the characteristics or features of the
various fragments of the immunoglobulin
molecule?
How is the specificity of an antibody “defined”
by the amino acid sequence of the
immunoglobulin molecule?
What features distinguish each immunoglobulin
class?
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