How do human leukocyte antigens affect organ transplant compatibility?

Human leukocyte antigens (HLA), which constitute the major histocompatibility complex in humans, are critical factors in organ transplant compatibility. These genetically determined cell-surface proteins act as markers that help the immune system distinguish between "self" and foreign substances.123

When an organ is transplanted, the recipient's immune system may recognize the donor's HLA molecules as foreign antigens, triggering an immune response that leads to graft rejection. Because HLA genes are highly variable, it is extremely rare for two individuals—other than identical twins—to share the same set of antigens.23

To minimize the risk of rejection, medical professionals perform tissue typing to identify and match the HLA antigens of the donor and recipient as closely as possible. A final safety measure, the direct crossmatch, tests the recipient's serum against donor lymphocytes to ensure no pre-existing antibodies will cause an immediate reaction. While close matching improves outcomes, many transplants rely on immunosuppressive drugs to manage the immune response when perfect compatibility is not possible.1423