Let us look at lymphocyte development, the
way that lymphocytes develop in the body.
The recognition of antigen by the immune system
occurs using four different types of molecule.
The Pattern Recognition Receptors which are present on
cell surfaces, inside cells and secreted or released
from cells, recognize Pathogen-Associated Molecular
Patterns and Damage-Associated Molecular Patterns.
We have maybe a small,
few hundred of these.
There are new ones being discovered
all the time, let’s say one or two hundred or so
different Pattern Recognition
Receptors that we each possess.
Each of these is
individually encoded by a gene.
So for each Pattern Recognition
Receptor we have a different gene,
and they are not very variable from one individual to another.
So for a given Pattern Recognition Receptor, probably your
Pattern Recognition Receptor’s exactly the same as mine.
Let’s say TLR4, probably your
TLR4 is exactly the same as mine.
In other words, they have low
polymorphism at the genetic level.
They don’t vary from one individual to another
for each individual Pattern Recognition Receptor.
Then we have the Major
Histocompatibility Complex molecules.
These are cell surface molecules
and each different MHC variant can
bind many different peptides derived
by processing of protein antigens.
And in each individual, there are around
about 12 different MHC molecules, with
respect to what we call the classical
MHC molecules, the main MHC molecules.
We each have about 12 of these.
Each protein is individually encoded.
So for MHC Class I in the human,
we have HLA-A, HLA-B, HLA-C.
For Class II we have HLA-DP, -DQ, -DR.
And each of those will have its own gene.
But at each gene locus, let’s say the HLA-A gene locus,
the sequence varies hugely from one individual to another.
So, my HLA-A molecules are probably
different to your HLA-A molecules.
And therefore, they are described as being extremely
polymorphic between one individual and another.
Then at the level of the cell surface of lymphocytes,
on T-cells, we have the T-cell receptor.
This molecule is highly specific for a
given combination of a peptide that is
produced by processing of protein antigen,
put together with MHC molecules.
So T-cell receptors are
highly peptide MHC specific.
And we can create millions and millions and
millions of different T-cell receptors.
Each of us can do that,
And this is due to a unique genetic
recombination mechanism to create diversity.
The B-cells have a similar
molecule on their surface.
It’s a different molecule encoded by different
genes, but in many ways it’s similar.
But on the B-cell surface, you
have a B-cell receptor or BCR.
But this molecule unlike the T-cell receptor
can also be released from B-lymphocytes.
So it’s produced in both the cell
surface and the secreted form, whereas
the T-cell receptor is only ever
produced in a cell surface form.
Antibody recognizes antigen in
a highly antigen specific way.
Just like we can produce millions of T-cell receptors, so we
can produce many millions of B-cell receptors and antibodies.
Okay, the B-cell receptor is simply a transmembrane
form on the cell surface of a B-cell.
And we can do this, just like we can for the T-cell receptors,
because of this unique genetic recombination mechanism.
So we have a bunch of T-cell receptor genes,
we have a separate bunch of B-cell receptor
genes or antibody genes, and these can recombine
by a mechanism that’s completely unique.
There’s nothing else in the body
does anything like this.
From a small number of genes,
a relatively small number of genes, we can
make millions and millions and millions
of different antigen receptors.
And it’s one of the things that makes the
adaptive immune response quite so remarkable.