Eivind Alhaug (eivind.alhaug at basalmed.uio.no) wrote:
: I'm simply wondering why we have a very large polymorfism on the HLA(MHC)-
: molecules.
: I'd appreciate any points of view.
The best explanation for this as of yet is a population genetics phenomenon
called balancing or overdominant selection. The products of these genes
play crucial roles in immune surveillance and response. Basically,
they are cell-surface molecules which bind peptides that are processed
within the cell and are displayed in a complex on the surface of certain
cells. These peptides are just naturally processed and can be seen by
certain OTHER cells (like CD4+ cells which are depleted in AIDS) as
"self" or "foreign". Foreign peptide/MHC complexes are seen as just that, and
removed from the body via immune response.
The pockets (part of the MHC molecule) which bind these peptides are
polymorphic in order to be able to process the broad range of potential
foreign invaders. The processes by which these genes have become so
highly polymorphic has been under considerable debate. Gene conversion
and recombination seem to play major roles in the generation of this
polymorphism. Polymorphism is maintained by the type of selection
I mentioned above (balancing/overdominant) which is basically
heterozygote advantage. An organism which can process more types
of antigens/peptides (a heterozygote) would have a better selective
advantage than an individual with a more limited repertoire (a
homozygote). In the worst case scenario, if a population were homozygous
at the loci encoded within the MHC (as would be the case in a
bottlenecked population such as the African cheetahs), if a major
pathogen came along of which it's processed peptides were not bound
or were poorly bound to the MHC molecule of the population, the entire
population could be easily wiped out.
Bottom line: It is harder to hit a moving target.
Hope this was some help, in a couple of paragraphs. If not, or if you
want more info, please write back. I have a zillion references, etc., if
you are interested
--
Meredith Yeager
Graduate Genetics Program
The George Washington Univeristy
Washington, D.C.
