Conservation of minor histocompatibility antigens between human and non‐human primates

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Abstract
It is well accepted that minor histocompatibility antigens (mHag) can function as transplantation barriers between HLA‐matched individuals. Little is known about the molecular nature and evolutionary conservation of mHag. It is only very recently that the first human mHag were identified. The HLA‐A2.1‐restricted mHag HA‐2 and the HLA‐B7‐restricted mHag H‐Y appeared to be peptides derived from polymorphic self proteins. Here we show that the HLA‐A2.1‐restricted mHag HA‐1, HA‐2, and the H‐Y peptides are conserved between man, chimpanzees and rhesus macaques. Human cytotoxic T cell clones specific for the HLA‐A2.1‐restricted mHag HA‐1, HA‐2, and H‐Y recognized HLA‐A2.1 gene‐transfected chimpanzee and rhesus macaque cells. Highpressure liquid chromatography fractionation of HLA‐A2.1‐bound peptides isolated from the HLA‐A2.1‐transfected chimpanzee cells revealed that the chimpanzee HA‐1 and HA‐2 co‐eluted with the human HA‐1 and HA‐2. Subsequent amino acid sequencing showed that the chimpanzee HA‐2 peptide is identical to the human HA‐2 peptide. Our functional and biochemical results demonstrate that mHag peptides are conserved for over 35 million years.