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I'd like to clear something up about antibodies that I'm not sure I've understood in the articles I've read. Looking at concepts such as "affinity maturation", "monovalent antigens" and "polyvalent antigens" it seems as if there are multiple antibodies which can bind to the same antigen. (Although I think I'm right in saying that individual antibodies can only bind to one antigen?) However, when I read sentences like "It has been estimated that humans generate about 10 billion different antibodies, each capable of binding a distinct epitope of an antigen" on the Wikipedia page (for antibody) it does make it sound like it's one antibody per antigen? Is this the case? Or is it one antibody per epitope. Either way, to put this question in a nutshell:

Is it true to say that the same substance could bind with (and, therefore, be recognised by) more than one antibody, or not?

Also, if the answer is no, does that mean that antibodies with different binding affinities are classed as the same antibody or not?

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Let's clarify the terms. An antigen is a molecule that can be associated with a particular substance (virus, pollen, dander.) When an immunoglobulin or antibody recognizes an antigen it binds to a specific epitope. An antibody recognizes an epitope using its paratope.

Some antigens have multiple epitopes; this means that different antibodies can simultaneously bind to them (if the epitopes are far-enough apart from each other so that binding to one doesn't preclude binding to the others.)

An example from my work is influenza (flu) hemagglutinin, which is a major viral coat protein. Here's a low-resolution structure showing a "head-binding" antibody fragment (actually three of them), and here's a similar structure showing a "stem-binding" antibody fragment. Our immune repertoire (and physiology) greatly predisposes us towards producing head-binding antibodies over stem-binders. Note that each structure has three antibody fragments bound in the same state. Because the head-binder and stem-binder antibodies are well-separated in space they can both be accommodated in a single complex (as is experimentally confirmed.) In this case, up to six antibodies, using two distinct paratopes, could simultaneously bind to a single antigen.

For matured (high affinity and high specificity) antibodies, each binds a specific epitope. The typical state of affairs is then explained "one antibody per epitope" which is overly simplistic because some epitopes can be recognized by multiple paratopes (which would be found on different antibodies.) So a given epitope can be recognized by no antibodies (a new antigen, or one that is poorly immunogenic) or by multiple ones.

Is it true to say that the same substance could bind with (and, therefore, be recognised by) more than one antibody, or not?"

Yes, that's true.

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    $\begingroup$ Is it, then, true that one paratope could bind to more than one epitope? $\endgroup$
    – Au101
    Commented Dec 29, 2013 at 2:14
  • $\begingroup$ Yes. The process of affinity maturation starts with low-affinity and low-specificity interactions, with the paratope getting progressively improved with respect to affinity and specificity. $\endgroup$
    – Ryan
    Commented Dec 29, 2013 at 7:18
  • $\begingroup$ Yes, this idea is called a polyclonal or polyspecific antibody. It is known that antibodies before they are fully matured are polyspecific. That is how we can recognize nearly limitless 'things' with only a limited number of antibodies. This is because each antibody you initially make can take on the job of binding more than one epitope. $\endgroup$
    – jwillis0720
    Commented Jan 10, 2014 at 23:53
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Yes -

Its all binding kinetics - even a monoclonal antibody will bind many different antigens. The affinity/avidity will be different depending on the interactions. The target antigen may have the lowest known K_d, but antibodies will still bind to many many other antigens. This is why when doing research using antibodies you often have to "block" your specimen with something like BSA or milk to try and reduce the "non-specific" binding.

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    $\begingroup$ Although right in principle, this idea is misleading. Yes it is true that at some equilibrium that you can bind anything, even if the Kd is 20 grams/ mL, but that's not adding to the discussion and really diluting it with semantics of concepts that are not physiologically relevant. $\endgroup$
    – jwillis0720
    Commented Jan 10, 2014 at 23:56

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