on- and off-rate of antibodies

Dima Klenchin klenchin at REMOVE_TO_REPLY.facstaff.wisc.edu
Wed Feb 2 12:12:39 EST 2000


In article <3896D7ED.22513AF0 at gengenp.rug.ac.be>, Esbjorn Fiers <esfie at gengenp.rug.ac.be> 
wrote:
>Dear all,
>I am working with scFv phage display libraries. In some articles I come
>across the words on- and off-rate, being the rate at which an antibody
>binds its antigen and the rate at which an antibody dissociates from its
>
>antigen. Furthermore, they say that when antibody affinities become
>higher this is mostly due to a lower off-rate, with the on-rate being
>less important. I kind of have problems to completely understand this.
>Is there anybody who could explain this to me, or has anyone a reference
>
>in which this is clearly explained?

This is the easiest way to understand it: 

ON rate for all biological reactions is, in first and very good approxymation,
a frequency of diffusional collision corrected by the geometrical factor (molecules
have to hit each other with "correct" sides which contain recognition sites). 
Imagine diffusiing spheres with pieces of Velcro attached to their sides - 
non-Velcro covered surfaces do not interact, covered do. There isn'ts much 
you can do to increase the frequency of them sticking to each other - you can't
increase diffusional coefficients and you cannot increase the surface covered 
with Velcro (because both are _given_ by design; unless you introduce some 
misterious long range forces). 

OFF rate is dictated by the strenght of this Velcro, however, and can be varied
dramatically from simple wool to superglue. Imagine that some demons 
constantly try to unstick each interacting pair and the time it takes them to do
so (off rate) will be dictated by a balance between Vecro's and Demon's strenght.
Thus, the off rate will be the main determinant of overall equilibrium constant 
(K=kon/koff). 

Hope this helps. 

        - Dima




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