Anti-MHC-peptide complex antibodies??

ladasky at ladasky at
Fri Oct 1 04:24:25 EST 1999

In article <C6NI3.71$F3.324 at uchinews>,
  kfrauwir at (Kenneth Frauwirth) wrote:
> In article <7sv492$hfi$1 at>,  <ladasky at> wrote:
> >In article <Pine.OSF.3.91.990929165822.20662A-100000 at>,
> >  nsharma at IMTECH.ERNET.IN (Naresh Sharma) wrote:
> >> Has anybody raised antibodies against MHC-peptide complex ?
> >> reply to
> >>
> >> naresh76 at
> >
> >There are many anti-MHC antibodies that recognize MHC complexed with
> >peptide.
> >
> >Or do you mean to ask whether there are antibodies against *specific*
> >peptides bound to *specific* MHC molecules?  Well, no, there are none
> >of those.  There are a few antibodies which recognize portions of the
> >alpha helices plus an amino acid or two of the peptide, but that's as
> >specific as they get.
> 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

John J. Ladasky Jr., Ph.D.
Department of Structural Biology
Stanford University Medical Center
Stanford, CA 94305

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