In organ transplantation, which factor is most important for reducing graft rejection?

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The most important factor is how closely the donor and recipient’s HLA antigens match. HLA proteins, part of the major histocompatibility complex, are what the immune system uses to distinguish self from non-self. T cells continuously monitor these molecules; when many HLA antigens are mismatched, the recipient’s T cells strongly recognize the graft as foreign and launch a rejection response. Hence, closer HLA matching between donor and recipient reduces this immune attack and improves graft survival. ABO compatibility is also important to prevent immediate hyperacute rejection, but even with a compatible blood type, poor HLA matching increases rejection risk. Donor age and the recipient’s baseline immune cell counts are less decisive factors in graft rejection compared with the degree of HLA compatibility.