Paper I
Question
Significance of MHC in transplantation.
Answer
The Major Histocompatibility Complex (MHC) — called the Human Leukocyte Antigen (HLA) system in humans — encodes cell-surface glycoproteins central to antigen presentation and self/non-self discrimination, making it the single most important genetic determinant of transplant compatibility.
Significance in transplantation:
- Graft rejection: MHC molecules on donor tissue are recognized as foreign (allogeneic) by the recipient’s T lymphocytes if donor and recipient MHC types differ — this recognition (direct or indirect allorecognition) triggers T-cell-mediated and antibody-mediated immune responses that attack and reject the graft. The degree of MHC mismatch between donor and recipient directly correlates with the intensity and speed of rejection.
- HLA matching: prior to transplantation (particularly for kidney and haematopoietic stem cell/bone marrow transplants), donor and recipient are typed and matched for key HLA loci (HLA-A, -B, and -DR are the most clinically important for solid organ transplant matching) — a closer match reduces the risk and severity of rejection and improves graft survival.
- Immunosuppression requirement: because complete HLA matching is rarely achievable outside identical twins, transplant recipients require long-term immunosuppressive therapy to prevent rejection, with the required intensity of immunosuppression generally correlating inversely with the degree of HLA match.
- Graft-versus-host disease (GVHD): in haematopoietic stem cell transplantation, MHC (HLA) disparity between donor and recipient also underlies the reverse phenomenon — donor T cells recognizing recipient MHC/tissue as foreign and attacking it — making HLA matching equally critical in this direction.
- Hyperacute rejection: pre-formed recipient antibodies against donor HLA (from prior sensitization — pregnancy, transfusion, previous transplant) can cause immediate, catastrophic hyperacute rejection, making pre-transplant cross-matching (testing recipient serum against donor lymphocytes) an essential screening step to exclude this risk before proceeding with transplantation.