The Minor Histocompatibility Antigen HA-1: A Diallelic Gene with a Single Amino Acid Polymorphism

TLDR

The minor histocompatibility antigen HA‑1 is the sole known mHag whose mismatch is linked to severe graft‑versus‑host disease after HLA‑identical bone marrow transplantation. Typing HA‑1 alleles in donors and recipients can refine donor selection and identify patients at high risk for HA‑1–induced GvHD. HA‑1 is a nonapeptide encoded by a KIAA0223 allele that differs by a single amino acid from its HA‑1–negative counterpart, and family analysis demonstrates a perfect correlation between this polymorphism and the HA‑1 phenotype.

Abstract

The minor histocompatibility antigen (mHag) HA-1 is the only known mHag for which mismatching is correlated with the development of severe graft versus host disease (GvHD) after human leukocyte antigen–identical bone marrow transplantation. HA-1 was found to be a nonapeptide derived from an allele of the KIAA0223 gene. The HA-1–negative allelic counterpart encoded by KIAA0223 had one amino acid difference from HA-1. Family analysis with HA-1 allele-specific polymerase chain reaction showed an exact correlation between this allelic polymorphism and the HA-1 phenotype. HA-1 allele typing of donor and recipient should improve donor selection and allow the determination of bone marrow transplantation recipients with high risk for HA-1–induced GvHD development.