Genes of interest in transplantation

MHC
The MHC is a highly conserved yet polymorphic gene locus. MHC molecules are surface proteins that present intracellularly processed peptides in a helical groove to their ligand, the T-cell receptor (TCR). Cognate interaction between an MHC molecule presenting peptide on an antigen-presenting cell and a specific TCR on a T cell can result in T-cell activation if the appropriate co-stimulatory molecules are present on the antigen-presenting cell. MHC class I molecules consist of three alpha domains and a b2 microglobulin chain, which is not encoded by the MHC gene locus. MHC class II molecules consist of two alpha domains and two beta domains. Peptides that are presented on the class I molecule are usually derived from intracellular proteins, whereas class II molecules present extracellularly derived peptides. The mechanism by which these peptides are transported to the immature MHC molecule is also very different for class I and class II MHC molecules, and has been recently reviewed in this journal (Ref. 7). The MHC is the major identification molecule that triggers allograft rejection, because it determines the difference between self (syngeneic) and non-self (allogeneic). When searching for a suitable organ donor, it is the MHC antigens that are matched between donor and recipient, to give the graft as good a chance as possible of functioning. In defined situations, this potency of the MHC has been exploited to tip the balance of the immune system from immunity to tolerance. The exposure of the recipient of a graft to donor MHC antigens before transplantation to induce tolerance was first investigated in a mouse model by Billingham and colleagues in 1953, when cells from a donor strain were introduced into a recipient mouse in utero