A human minor histocompatibility antigen specific for B cell acute lymphoblastic leukemia

Human minor histocompatibility antigens (mHags) play an important role in t he induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia af ter human histocompatibility leukocyte antigen (HLA)-identical allogeneic b one marrow transplantation (BMT). As most mHags are not leukemia specific b ut are also expressed by normal tissues, antileukemia reactivity is often a ssociated 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 H B-1-specific CTLs. Interestingly, expression of the HB-1 gene was only obse rved in B-ALL cells and Epstein-Barr virus-transformed B cells. The HB-1 ge ne-encoded peptide EEKRGSLHVW is recognized by the CTL in association with HLA-B44. Further analysis reveals that a polymorphism in the HB-1 gene gene rates a single amino acid exchange from His to Tyr at position 8 within thi s 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-A LL cells and the ability to generate MB-1-specific CTLs in vitro using pept ide-loaded dendritic cells offer novel opportunities to specifically target the immune system against B-ALL without the risk of evoking GVHD.