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SUMMARY:Affinity maturation of antibodies targeting HIV spikes - Mehran Ka
 rdar\, Massachusetts Institute of Technology
DTSTART:20231214T130000Z
DTEND:20231214T140000Z
UID:TALK206668@talks.cam.ac.uk
CONTACT:Marco Vona
DESCRIPTION:Affinity maturation (AM) is the process through which the immu
 ne system evolves antibodies (Abs) which efficiently bind to antigens (Ags
 )\, e.g. to spikes on the surface of a virus. This process involves compet
 ition between B-cells: those that ingest more Ags receive signals (from T 
 helper cells) to replicate and mutate for another round of competition. Mo
 deling 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 structur
 e of the antibody). We argue that\, to evade the immune system\, most viru
 ses evolve high spike densities (SDs). An exception is HIV whose SD is two
  orders of magnitude lower than other viruses. However\, HIV also interfer
 es 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 w
 hen SD is high\, but not if SD is low. This special feature of HIV infecti
 on may have led to the evolution of a low SD to avoid potent immune respon
 ses early on in infection. Our modeling also provides guides for design of
  vaccination strategies against rapidly mutating viruses.
LOCATION:MR12\,  Centre for Mathematical Sciences\, Wilberforce Road\, Cam
 bridge
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