Anti-MHC-peptide complex antibodies??

Mike Clark mrc7 at cam.ac.uk
Fri Oct 1 12:10:24 EST 1999


In article <0J4J3.125$F3.1656 at uchinews>, Kenneth Frauwirth
[snip]
> 
> And the same is true of just about *any* antibody-antigen interaction -
> there will be side-chains and functional groups which don't interact with
> the Ab, and can be substituted.  With that said, why do you think that
> the TCR would necessarily be more sensitive to polymorphism than an
> antibody?  TCR repertoire is restricted far more highly than Ab by
> selective processes, and appears to be genetically pre-selected for a
> specific type of interaction with the MHC.  Antibody generation does not
> have the same restrictions, and so some may interact with higher sequence
> specificity than TCRs.
> 
> In any case, like with the TCR, the substituted peptides which might give
> false positives are rarely present in assays unless intentionally added
> (although I'm aware that it can happen - it cost a post-doc in my old lab 
> several months of work to learn that the expression library he was using
> to clone out T cell antigens accidentally generated just such a
> cross-reactive peptide),  and so the anti-peptide/MHC Abs are de facto
> specific for the peptide used to raise them.
> 
> Ken Frauwirth

Your points are well made Ken. The problem with what the antibody
recognises is not so much what it is capable of recognising but is more
a problem of the frequency of obtaining antibodies of a given property
coupled with the screening and or selection process. Obviously in T-cell
receptors most of the variability is combinatorial and tends to focus major
differences in CDR3. Whilst this is also true in antibodies the additional
somatic mutation allows for the CDR1 and CDR2 and also all of the framework
regions to 'drift' away from the inherited germline sequences. 

Mike Clark,                        <URL:http://www.path.cam.ac.uk/~mrc7/>
-- 
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