Identification of a Graft Versus Host Disease-Associated Human Minor Histocompatibility Antigen

TLDR

Minor histocompatibility antigen disparities between HLA‑matched bone marrow donors and recipients are a major risk factor for graft‑versus‑host disease, as illustrated by a previously isolated HLA‑A2.1‑restricted cytotoxic T‑cell clone recognizing HA‑2 in a patient with severe GVHD. Because HA‑2 has a phenotype frequency of 95 % in the HLA‑A2.1‑positive population, it is a candidate for immunotherapeutic intervention in bone marrow transplantation. The HLA‑A2.1‑bound peptide representing HA‑2 has now been identified and appears to originate from a member of the non‑filament‑forming class I myosin family.

Abstract

Minor histocompatibility antigen disparities between human leukocyte antigen (HLA)-matched bone marrow donors and recipients are a major risk factor for graft versus host disease (GVHD). An HLA-A2.1-restricted cytotoxic T cell clone that recognized the minor histocompatibility antigen HA-2 was previously isolated from a patient with severe GVHD after HLA-identical bone marrow transplantation. The HLA-A2.1-bound peptide representing HA-2 has now been identified. This peptide appears to originate from a member of the non-filament-forming class I myosin family. Because HA-2 has a phenotype frequency of 95 percent in the HLA-A2.1-positive population, it is a candidate for immunotherapeutic intervention in bone marrow transplantation.