Abstract
The matching of the major histocompatibility antigens (HLA) was thought to be the most important factor in the prognosis of stem cell transplantation (SCT). The resultant nationwide SCT data, which is accumulated and analyzed, demonstrates that the minor histocompatibility antigens (mHa) is no longer a minor factor, but a major one for GVHD after SCT. In fact, the incompatibilities of mHas are radically lower, approximately half, in relatives than in nonrelatives. The discovery of long-term feto-maternal microchimerism became an essential issue for the development of the concept of immunotolerance against non-inherited maternal antigens (NIMA). Mitochondria DNAs are highly polymorphic, and thus their proteins must be sources of mHas. Mother and child siblings have identical mitochondria and also NIMA tolerance. This is found to be because the donors who are HLA haploidentical mismatch maternal, and NIMA mismatched siblings are more compatible than paternal, viz. NIPA (non-inherited paternal antigens) mismatched siblings, and nonrelatives. Consequently, from the viewpoint of the contemporary histocompatibility concept, it is necessary to consider not only HLA and mHa, but also mitochondria, feto-maternal immunotolerance, and NIMA incompatibility in siblings.
