Let us look at the structure
of an antibody molecule.
They consist of two identical heavy chains,
each of which is about 50 kilo Daltons in size.
And two identical light chains, each of which
is around about 25 kilo Daltons in size.
So adding those together, we can see that the basic
antibody molecule is around about 150 kilo Daltons.
They vary a little bit from class to class, but that
basic structure is around about 150 kilo Daltons.
The two heavy chains are linked
to each other by a disulfide bond.
And each light chain is disulfide
bonded to one of the heavy chains.
This creates a very stable structure.
Remember disulfide bonds are covalent
bonds that are essentially irreversible.
The antibody can be divided into two different parts
- the Variable region and the Constant region.
So here we can see the
Variable region highlighted.
And this is the part that varies from
one antibody to another as the name
suggests, and of course that’s related
to the specificity of the antibody.
In other words, to antigen binding.
In contrast, the Constant regions
of the antibody, particularly of the
heavy chain are involved in the
effector function of the antibody.
That means what the antibody is actually going to go on
and do in order to get rid of the particular infection.
We can also divide the antibody up into what are called
the Fab fragments - the Fragment antigen binding.
Here, one of the Fragment antigen
binding areas is indicated.
And there are a total of two Fabs.
And a Fragment crystallizable or Fc fragment which comprises
the majority of the Constant region of the heavy chains.
So here you can see the two Fabs and the
Fc that comprise an antibody molecule.
The light chain Constant region can either be a kappa
light chain Constant region or a Lambda light chain.
And because the two heavy chains in a single antibody molecule
are identical to each other, and the two light chains are
identical to each other, if one of the light chains is a
lambda light chain, the other will be a lambda light chain.
If one’s a kappa light chain, the
other will be a kappa light chain.
You never get a mixture of two different types
of light chain in a single antibody molecule.
In terms of the different classes or isotypes of antibodies,
this is determined by the heavy chain Constant region.
So the mu heavy chain specifies that the
antibody is an IgM class of antibody.
It’s what’s defining it as an IgM.
We call an antibody with a C mu
Constant region, an IgM antibody.
If it has a delta Constant region in the heavy chain,
that defines it as being an IgD class of antibody.
Gamma would be IgG, and in fact there are four
subclasses of IgG : IgG1, IgG2, IgG3 and IgG4.
Alpha heavy chain Constant region
classifies the antibody as being IgA.
And there are two subclasses
of IgA: IgA1 and IgA2.
And then finally, if the Constant region of the heavy chain
is a C epsilon region, then it’s an IgE antibody.
The immunoglobulin heavy chain and the immunoglobulin
light chain are folded up into domain type structures.
The light chains have two domains: one
Variable domain and one Constant domain.
Whereas the heavy chains also have a single Variable domain,
and then have either three or four Constant domains.
An antibody molecule with three Constant domains for the
heavy chain is shown in this particular image.
And IgG, IgA and IgD antibodies each have three Constant
domains in their heavy chain, whereas IgM and IgE
antibodies have an additional Constant region domain, making
a total of four Constant domains in each heavy chain.
The way in which these polypeptide
chains are folded, the heavy and
the light chain of the antibody
molecule can be seen on this diagram.
So here we have the Variable domain of the light
chain and the Constant domain of the light chain
folded into this domain type structure which is
stabilized by disulfide bonds within the chain.
What we refer to as intra-chain
disulfide bonds - within the chain.
And the heavy chain here, you can see again, folded up
into one Variable domain and three Constant domains.
Between the CH1 domain and the CH2 domain,
there is an area that is called the hinge.
This gives flexibility
to the antibody molecule.
The two arms of the antibody molecule can move
in order to facilitate binding to the antigen.
And here you can see the complete antibody molecule
with the other heavy chain and the other light chain.
And at the tip, the antigen binding site, made up from the
VH domain and the VL domain of each antigen binding arm.
Looking in a little bit more detail at exactly how the protein
is folded, we can see that it has this very typical structure.
And in fact, this is called an
immunoglobulin domain type structure.
And it’s found in many, many different molecules
in the body, not just immunoglobulins.
But it was first discovered in immunoglobulins, which
is why it’s called an immunoglobulin type domain.
And the immunoglobulins remember, is the
biochemical term if you like for antibodies.
So here we have a light chain, the Constant region of the
light chain and the Variable region of the light chain.
Both folded up into this
immunoglobulin type domain structure.
Importantly what you can see here, highlighted in blue, is
the three hypervariable regions within the Variable region.
In other words, the Complementarity Determining
Regions or CDRs - CDR1, CDR2 and CDR3.
And they’re called Complementarity Determining
Regions because the amino acids within
these CDRs are complementary to amino acids in
the antigen that is going to be recognized.
And illustrated here is the CDR distribution within the light
chain Variable region and the heavy chain Variable region.
So in total, there are six CDRs in each antigen
binding site; three of them coming from the
Variable region of the heavy chain and three of
them from the Variable region of the light chain.
You can see the antigen binding to one arm, and the
other arm will bind an identical copy of the antigen.
Remember, because the two heavy chains are
identical to each other, the two light chains are
identical to each other, the antigen binding
specificity of the two arms - absolutely identical.