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

Joke M. M. den Haan, Nicholas E. Sherman, Els Blokland, Eric L. Huczko, Frits Koning, Jan W. Drijfhout, Jonathan Skipper, Jeffrey Shabanowitz, Donald F. Hunt, Víctor H. Engelhard,

Science · 1995 · 417 citations · 36 references

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TL;DR

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.

References

36