In article <bohmfalk-1105960753380001 at pm1-7.tcgcs.com>, John Bohmfalk
<mailto:bohmfalk at tcgcs.com> wrote:
> I have some questions concerning CTL recognition of allograft MHC-I
> molecules. CTL killing is normally MHC-I restricted, but allografts
> obviously possess non-self MHC. One idea presented in an immunology text
> is that a large percentage (20% or so) of TCR on CTL are able to
> cross-react sufficiently with non-self MHC to result in killing of the
> allograft.
>> If this is the case, and if this cross-reaction of TCR with non-self MHC-I
> is an important mechanism in at least the initiation of graft rejection,
> then it would seem that the more similar the MHC are, the more easily the
> graft would be rejected. This would imply that careful, but not exact,
> MHC matching might be somewhat counterproductive.
>> Where am I wrong or confused or ignorant?
>> Thanks in advance for your comments, either posted or emailed.
>> John
Well your conjecture is not completely wild. There are many transplant
surgeons who do not bother to tissue match their organ grafts in advance
of the transplant. The statistics on survival do seem to suggest that
sometimes a distantly related or uncommon tissue type has a better
chance of survival.
Obviously although one's own T-cells are restricted to one's own MHC the
TCR repertoire of every individual has the capacity to generate MHC
restricted TCR for any human MHC haplotype. This potential has to be there
in the system because the MHC and TCR are inherited in seperate linkage
groups. The sequence/structural variation of MHC molecules makes it
quite likely that one allele of MHC plus a given peptide may look
similar to another allele plus a different peptide. Thus with the large
number of T-cells within a given individual it is not unexpected to find
cross reactions on other MHC peptide combinations.
I think the major problem with your argument though is that we do not know
how many alloreactive T-cell clones it requires to reject an allograft.
Obviously if only one clone is required it makes little difference if the
frequency of that cross-reactive clone is 1 in 5 (your 20% figure) or
1 in 5 million. Thus although the frequency of cross reactions may
vary with different MHC types, the lower frequencies are still finite
and significant within the context of an immune response.
Mike Clark, mrc7 at cam.ac.ukhttp://www.path.cam.ac.uk/~mrc7/
--
o/ \\ // || ,_ o Dr. M.R. Clark, Division of Immunology
<\__,\\ // __o || / /\, Cambridge University, Dept. Pathology
"> || _`\<,_ // \\ \> | Tennis Court Rd., Cambridge CB2 1QP
` || (_)/ (_) // \\ \_ Tel. 01223 333705 Fax. 01223 333875
