J. Exp. Med., Volume 189, Number 2, January 18, 1999 301-308

A Human Minor Histocompatibility Antigen Specific for B Cell Acute Lymphoblastic Leukemia

By Harry Dolstra,^* Hanny Fredrix,^* Frans Maas,^* Pierre G. Coulie,^§ Francis Brasseur, Ewald Mensink,^* Gosse J. Adema, Theo M. de Witte,^* Carl G. Figdor, and Elly van de Wiel-van Kemenade^*

From the ^* Department of Hematology and the  Department of  Tumor Immunology, University Hospital Nijmegen, 6500 HB Nijmegen, The Netherlands; and the ^§ Cellular Genetics Unit and the  Ludwig Institute for Cancer Research, Université Catholique de Louvain, B-1200 Brussels, Belgium

Human minor histocompatibility antigens (mHags) play an important role in the induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen (HLA)-identical allogeneic bone marrow transplantation (BMT). As most mHags are not leukemia specific but are also expressed by normal tissues, antileukemia reactivity is often associated with life-threatening graft-versus-host disease (GVHD). Here, we describe a novel mHag, HB-1, that elicits donor-derived CTL reactivity in a B cell acute lymphoblastic leukemia (B-ALL) patient treated by HLA-matched BMT. We identified the gene encoding the antigenic peptide recognized by HB-1-specific CTLs. Interestingly, expression of the HB-1 gene was only observed in B-ALL cells and Epstein-Barr virus-transformed B cells. The HB-1 gene-encoded peptide EEKRGSLHVW is recognized by the CTL in association with HLA-B44. Further analysis reveals that a polymorphism in the HB-1 gene generates a single amino acid exchange from His to Tyr at position 8 within this peptide. This amino acid substitution is critical for recognition by HB-1-specific CTLs. The restricted expression of the polymorphic HB-1 Ag by B-ALL cells and the ability to generate HB-1-specific CTLs in vitro using peptide-loaded dendritic cells offer novel opportunities to specifically target the immune system against B-ALL without the risk of evoking GVHD.

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