IgG - IgG interactionS...

Mike Clark mrc7 at cam.ac.uk
Fri May 21 06:42:05 EST 1999

In article <Pine.A41.4.10.9905201917210.79322-100000 at dante21.u.washington.edu>,
F. Hayashi <URL:mailto:hayashi at u.washington.edu> wrote:
> On Thu, 20 May 1999, Greg Adams wrote:
> > Antibodies that react to the antigen binding domain (CDRs) of another
> > antibody are typically called anti-idiotype antibodies.  This occurs
> > naturally in people and a chain reaction type of effect can occur with
> > the antibody (#2) that binds to the antigen binding domain of the first
> > antibody (#1), mimicing the original antigen target of the first
> > antibody.  The second antibody then can actually initiate an immune
> > response that will recognize the original antigen.  Similar strategies
> > are being employed in clinical trials to try to stimulate patients to
> > mount an immune response to tumor antigens.
> Ahhh.  I had a prof in my undergraduate days (Eli Sercarz) that was really
> into Niels Jerne's idiotype cascade idea.
> I'm sure that antibodies CAN be anti-idiotype, but I wonder about the
> biological significance of it....
> Is anyone aware of any published research that shows significance of
> anti-idiotype antibodies?

I can't help rising to the bait here as it connects quite nicely with
another posting of mine to this news group and I'd like to hijack the
thread. (However I doubt if it is the example which you intended!)

One 'significance' of 'anti-iditoype antibodies' is that they can seriously
screw up the efficacy in use of therapeutic monoclonal antibodies. Once a
patient develops an anti-idiotype response it is usually impossible to
carry on with the therapy. 

Now why I have risen to the bait is that as the posting above hinted at
there is very good evidence for natural idiotype anti-iditype recognition
even for antibodies from the same test animal or patient. Currently however
there is a lot of publicity about 'fully human' antibodies made from phage
libraries or from transgenic mice (See for example advertisments in
Immunology Today). Various prominent scientists and also commercial
organisations are claiming that because they are 'fully' human sequences
that the antibodies so produced will not be immunogenic in human patients.

As an immunologist my answer to this is just look at the facts!

1) Anti-idiotypic reactions can and do occur even in a single individual.
They have been demonstrated in many different studies.

2) There are many examples of autoimmune reactions to endogenous 'self'

3) There are many reasons to modify the concept of 'self' vs 'non-self'
recognition in favour of including ideas of 'danger' vs 'non-danger'.

My arguments are of course independent of whether you believe in a natural
role for idiotypic networks in maintaining the B-cell or T-cell repertoire.

Mike Clark,                        <URL:http://www.path.cam.ac.uk/~mrc7/>
 o/ \\    //            ||  ,_ o   M.R. Clark, PhD. Division of Immunology
<\__,\\  //   __o       || /  /\,  Cambridge University, Dept. Pathology
 ">    ||   _`\<,_    //  \\ \> |  Tennis Court Rd., Cambridge CB2 1QP
  `    ||  (_)/ (_)  //    \\ \_   Tel.+44 1223 333705  Fax.+44 1223 333875

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