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Hello, I'm Anton Van der Merwe from the University of Oxford,
and I'm going to be talking about affinity,
avidity, and kinetics in immune recognition.
Here's an overview of my lecture.
After this introduction, I'll be talking about the key binding concepts,
discussing measuring binding properties,
and then finish by discussing the special features of cell surface molecules.
Now immune recognition is driven by protein-ligand interactions,
and the proteins and ligands can either be soluble or surface-associated.
A particular challenge for immune recognition is that the ligands e.g,
the antigens often arise from infectious organisms or cancer cells.
They are very diverse and can evolve rapidly.
To meet this challenge, the recognition proteins also
need to be very diverse and to be able to evolve rapidly.
Now the binding properties such as the affinity and kinetics of
immune protein-ligand interactions or what determines the functional outcome of binding.
Understanding these properties and how they measured
is important for understanding immune responses.
Antigen recognition involves hugely diverse, somatically generated,
and clonally expressed T and B cell antigen receptors,
also called TCR receptors and antibodies.
These develop on T and B cells during their development,
and this development includes
positive and negative selection events that depend
on the affinity of these receptors for self-antigen.
Now each TCR receptor on a maturity cell combine multiple similar ligands and
needs to able to discriminate between them based
on subtle differences in affinity and kinetics.
TCRs receptors and primary antibodies actually have quite low affinity for the ligand.
This isn't a problem for TCR receptors because TCR receptors and their ligands are
on cells and recognition that a cell-cell interface can tolerate low affinities.
It is a problem however for antibodies.
Primary antibodies compensate for the low-affinity
by increasing the valency of binding or the avidity,
and antibodies can undergo affinity maturation to
become high-affinity secondary antibodies.