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Why are human leukocyte antigens important in organ transplantation?

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Illustration of a blood vessel with a cutaway view showing red blood cells, white blood cells, platelets, and plasma, each labeled to highlight the main components of blood. — white blood cell Blood is made up of multiple components, including red blood cells, white blood cells, platelets, and water-rich plasma.

Human leukocyte antigens (HLA) are critical in organ transplantation because they serve as the primary markers the immune system uses to distinguish "self" from "nonself". These cell-surface proteins, which are part of the major histocompatibility complex, act as antigens that can trigger an immune response if they are recognized as foreign.12

When an organ is transplanted, the recipient's immune system—specifically T lymphocytes—may identify the donor’s HLA molecules as foreign and initiate a rejection response, leading to the destruction of the graft. Consequently, tissue typing is performed to identify an individual's HLA antigens and find a donor whose tissue type matches the recipient as closely as possible.314

Matching is essential to minimize the risk of rejection and, in cases such as bone marrow transplants, to reduce the likelihood of graft-versus-host disease, where donor cells attack the recipient's tissues. Because HLA genes are highly variable, finding a perfect match is difficult, making tissue compatibility a central challenge in successful transplantation.5241