Speaker
Mehran Kardar
Description
Affinity maturation (AM) is the process through which the immune
system evolves antibodies (Abs) which efficiently bind to antigens
(Ags), e.g. to spikes on the surface of a virus. This process involves
competition between B-cells: those that ingest more Ags receive
signals (from T helper cells) to replicate and mutate for another round
of competition. Modeling this process, we find that the affinity of the
resulting Abs is a non-monotonic function of the target (e.g. viral spike)
density, with the strongest binding at an intermediate density (set by
the two-arm structure of the antibody). We argue that, to evade the
immune system, most viruses evolve high spike densities (SDs). This is
indeed the case, except for HIV whose SD is two orders of magnitude
lower than other viruses. However, HIV also interferes with AM by
depleting T helper cells, a key component of Ab evolution. We find that
T helper cell depletion results in high affinity antibodies when SD is
high, but not if SD is low. This special feature of HIV infection may
have led to the evolution of a low SD to avoid potent immune
responses early on in infection.
Primary author
Mehran Kardar
