MHC restriction

Ian A. York iayork at
Fri Feb 28 12:01:02 EST 1997

In article <3316041F.2451 at>, Ken Miyasaki  <kmiyasak at> wrote:
>I was just curious as to how immunologists viewed "MHC restriction."
>Does it really exist? Isn't it just a laboratory artifact (based upon
>measurement of secondary immune responses)? Doesn't the TCR see mainly
>the antigen and not the MHC (with greater than three orders of magnitude
>difference in affinity). So why was the 1996 Nobel Prize awarded to
>people who proposed this dual cognition stuff?

I'm not sure what you're talking about.  TcR sees the combination of
epitope and MHC.  With the wrong MHC the affinity is unmeasurable.  This
is not a laboratory artifact; it's fundamental to the structure of the
TcR and profoundly important.  

If you look at crystal structures of MHC/peptide, then you'll see that
almost all the face of the interaction that the TcR sees is foirmed by the
MHC.  The peptide provides critical alterations in the structure, but in
many cases this is a relatively small component of the interaction
surface.  (Check out the recent crystal structures of the TcR/MHC
interaction from Wiley's and from Wilson's labs.)

In fact, it's much more true to say the reverse of your statement.  Where
there's wobbliness in the TcR recognition, it's likely to be with the same
MHC and with different peptide.  

To summarize, I think you are confused about TcR recgnition.  I'm not sure
what you mean by your statement, but it's wrong.

The Nobel was well-deserved, as far as I'm concerned.  I'm sure this will
come as a relief to the Nobel Committee.

      Ian York   (iayork at  <>
      "-but as he was a York, I am rather inclined to suppose him a
       very respectable Man." -Jane Austen, The History of England

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