Why will MHC indicate graft as foreign?
Ian A. York
iayork at panix.com
Tue Jul 8 06:41:16 EST 2003
In article <noemail-42FD4D.23464007072003 at cnews.newsguy.com>,
Hobo <noemail at noemail.com> wrote:
>strings they may sample. This means the total number of MHC/protein
>possibilities is extraordinarily large. How do the white blood cells
>recognize such a large number of possibilities?
Lymphocyte receptors (antibody and T cell receptor) are extraordinarily
diverse. This diversity is produced, in general, by shuffling multiple
DNA segments during their differentiation. The various potential
combinations add up to a number that is large enough to handle all the
possible MHC/peptide combinations in the universe.
It's also worth noting that in recent years, we've come to appreciate that
there's a significant amount of overlap. The classic concept of one T
cell receptor, one peptide/MHC complex, is not correct; a single TcR can
see many peptide/MHC complexes, albeit not always with equal efficiency.
>I've read that cancer cells downregulate MHC expression, often to zero.
>NK cells are programmed to kill cells with zero MHC expression. I've
>read that the cancer cells avoid this by expressing MHC homologs at the
>surface, fooling the NK cells. If the immune system can be fooled so
>easily by MHC homologs, why is it so sensitive to differences in MHC
>composition between native and donated tissue?
Cancer cells probably don't express MHC homologues. However, your general
point may be right, because it's possible that some viruses that
downregulate MHC class I do express MHC class I homologues (e.g.
cytomegalovirus). The function and mechanism of these homologues isn't
quite clear, and that's true for viral immune evasion in general. Viruses
(as opposed to cancer cells) *may* only have to delay recognition and
killing, rather than avoid it forever, so that the virus can complete
replication within the cell--from the virus's viewpoint, postponing
recognition by a few hours may be all it needs to do.
These mechanisms, whether viral or tumour, don't operate in isolation.
Cancer cells are the product of many rounds of selection, so that the
established tumours you see are the best survivors out of billions or
trillions of precursors clones that were killed by immune responses. Even
viruses, with their much-simpler genomes, have subtle and effective
combinations of immune evasion approaches, all working together.
Or, in other words, we don't know.
Ian York (iayork at panix.com) <http://www.panix.com/~iayork/>
"-but as he was a York, I am rather inclined to suppose him a
very respectable Man." -Jane Austen, The History of England
More information about the Immuno