Antibody's specifity...

Mike Clark mrc7 at
Wed Jul 23 10:51:56 EST 2003

In article <3F1D3F00.3030707 at>, Bryan Heit
<URL:mailto:bjheit at> wrote:
> Nikolai Scherbak wrote:
> > Dear colleagues! 
> > Can antibodies raised against one protein bind also to another protein
> > with the 50% similarity to the first one?
> >
> >Sincerely, Nikolai
> >
> >---
> >  
> >
> Highly unlikely.  Antibodies are very specific, and often can 
> differentiate between isoforms with less then 1% difference.  Your only 
> hope would be if there was an identical shared domain between your two 
> proteins of interest.  An antibody raised against that domain may be 
> cross reactive, assuming of course the rest of the protein doesn't 
> produce a steric hindrance, or induce different folding of the domain.
> Bryan

I disagree! 

Antibodies may or may not be "specific" depending upon how they
are selected and how in practice you define specificity. Specificity is not
an absolute universal concept. In most cases antibody specifity is defined
for a narrow application based on emprical observation. e.g. "In ELISA
assays my antibody only binds to antigen A but not to control antigens B,
C, or D."

The physiological specificity of an antibody usually results from both a
positive selection of B-cells on one antigen and negative selection on
others. The most commonly encountered negative selection in-vivo is
negative selection for autoreactivity.

So the answer to the original question posed by Nikolai above is, yes,
under some circumstances.

Also all antibodies have the potential to bind a large number of different
antigens and thus specificity can easily be seen to be  a "relative"
concept.  You can illustrate this principle with a simple thought
experiment. For example if you take an antibody to any given antigen, and
then you raise a series of different anti-idiotype antibodies to that first
antibody, you essentially have a whole family of different antigens all
with binding affinity to the same antibody.

Mike                             <URL:>
M.R. Clark, PhD. Division of Immunology
Cambridge University, Dept. Pathology
Tennis Court Rd., Cambridge CB2 1QP
Tel.+44 1223 333705  Fax.+44 1223 333875

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