You’ll now look at the way in which a signal is sent
into the B-cell in order to achieve B-cell activation.
Along with the transmembrane version of antibody on the surface
of the B-cell, there are the Ig-alpha (Ig-α) and Ig-beta
(Ig-β) molecules with their cytoplasmic tails containing
Immunoreceptor Tyrosine-based Activation Motifs or ITAMS.
But that isn’t the entirety of the B-cell receptor
because it’s also associated with other molecules.
It’s associated with a B-cell co-stimulatory complex,
and this consists of several different molecules.
Leu13, CD21 which is also actually referred to
as complement receptor 2 because it is indeed a
complement receptor, CD19 which again importantly
has ITAMs in its cytoplasmic tail, and CD81.
So these four molecules, Leu13, CD21, CD19 and CD81 form
the B-cell co-stimulatory complex, which together with
the transmembrane version of antibody and the Ig-α and
the Ig-β molecules are required for B-cell activation.
If the B-cell has an antibody on its surface
that is capable of recognizing a particular
antigen; so let’s say that this is a Cytomegalovirus
and the B-cell encounters Cytomegalovirus,
then what happens is that the antibody will
bind to the antigen that it is specific for and
more than one B-cell receptor molecule will
link together, be cross linked by the antigen.
They’ll come together, and this will drag those
ITAMs in Ig-α and Ig-β nearer to each other.
And that cross linking of these
antibodies by antigen, and therefore the
aggregation of the Ig-α and Ig-β
together with the B-cell stimulatory
complex will lead to protein kinases
such as Lyn kinase phosphorylating
the tyrosines on the Immunoreceptor
Tyrosine-based Activation Motifs.
And this phosphorylation by kinases will initiate a signaling
cascade that ultimately results in
activation of the B-lymphocyte.
So that’s how B-lymphocytes
What about T-lymphocytes?
Well, it’s a very similar situation.
Here we have a T-cell receptor
on the surface of a T-lymphocyte.
This is associated with the CD3 molecules, CD3 gamma
(CD3γ), CD3 delta (CD3δ) and CD3 epsilon (CD3ε).
And they all have within their
cytoplasmic region, ITAMs.
Also there will be a homodimer of two
zeta chains, again containing ITAM motifs.
This particular T-cell
is a CD4+ T-cell.
So the CD4 molecule will also be
present as part of this complex.
When the T-cell receptor recognizes the peptide MHC
Class II combination that its specific for; and remember
CD4+ T-cells recognize MHC Class II molecules, whereas
CD8+ T-cells recognize MHC Class I molecules.
So following this interaction, if the
T-cell is specific for that particular
peptide MHC Class II combination, various
protein kinases including the Lck kinase
can add phosphate groups to the tyrosines
in the ITAMs; again, initiating a
signaling cascade that will ultimately
result in activation of the T-lymphocyte.
Of course, not all T-cells are CD4+
T-cells, some of them are CD8+ T-cells.
And the situation is very, very similar
with the CD8+ T-cell, shown here,
using its T-cell receptor to recognize
a peptide MHC Class I combination.
But the signaling events are pretty much
identical to those seen with the CD4+ T-cell.