Anti-MHC-peptide complex antibodies??

Kenneth Frauwirth kfrauwir at midway.uchicago.edu
Fri Oct 1 10:48:12 EST 1999


In article <7t1uk2$jmj$1 at nnrp1.deja.com>,  <ladasky at my-deja.com> wrote:
>In article <C6NI3.71$F3.324 at uchinews>,
>  kfrauwir at midway.uchicago.edu (Kenneth Frauwirth) wrote:
>>
>> There is an antibody called Y-Ae, generated by Rudensky/Janeway, which
>> recognizes a peptide from the I-E alpha chain complexed to the I-A(b)
>> molecule, and another called 30-2 generated by Morkowski/Rudensky,
>> which recognizes a peptide from murine invariant chain bound to I-A(b).
>> I believe there is also an antibody against the SIINFEKL/K(b) complex.
>
>But what, exactly, is being recognized?
>
>I'm willing to bet that you can make all kinds of substitutions in the
>buried residues of the peptide -- and as long as the peptide still binds
>MHC, you will almost certainly obtain antibody binding.  I can't imagine
>that a mAb would be any more sensitive to peptide polymorphism than the
>TCR itself.  And, in fact, mAb specificity for peptide residues has been
>tested in at least one case.  See Huang F et. al., Infect Immun 64:120-7
>[1996].

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
-- 
Ken Frauwirth (MiSTie #33025)  kfrauwir at midway.uchicago.edu
Abramson Cancer Research Institute
University of Pennsylvania
http://mail.med.upenn.edu/~kfrauwir



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