B- and T-Cell Activation – Lymphocyte Activation

00:01 You’ll now look at the way in which a signal is sent into the B-cell in order to achieve B-cell activation.

00:12 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.

00:31 But that isn’t the entirety of the B-cell receptor because it’s also associated with other molecules.

00:42 It’s associated with a B-cell co-stimulatory complex, and this consists of several different molecules.

00:48 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.

01:07 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.

01:28 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.

01:56 They’ll come together, and this will drag those ITAMs in Ig-α and Ig-β nearer to each other.

02:05 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.

02:30 And this phosphorylation by kinases will initiate a signaling cascade that ultimately results in activation of the B-lymphocyte.

02:41 So that’s how B-lymphocytes become activated.

02:43 What about T-lymphocytes? Well, it’s a very similar situation.

02:47 Here we have a T-cell receptor on the surface of a T-lymphocyte.

02:52 This is associated with the CD3 molecules, CD3 gamma (CD3γ), CD3 delta (CD3δ) and CD3 epsilon (CD3ε).

03:00 And they all have within their cytoplasmic region, ITAMs.

03:05 Also there will be a homodimer of two zeta chains, again containing ITAM motifs.

03:13 This particular T-cell is a CD4+ T-cell.

03:17 So the CD4 molecule will also be present as part of this complex.

03:24 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.

03:44 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.

04:09 Of course, not all T-cells are CD4+ T-cells, some of them are CD8+ T-cells.

04:15 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.

04:27 But the signaling events are pretty much identical to those seen with the CD4+ T-cell.