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

Université catholique de Louvain, Лувен-ла-Нев, Wallonia, Belgium
Journal of Experimental Medicine (Impact Factor: 12.52). 02/1999; 189(2):301-8. DOI: 10.1084/jem.189.2.301
Source: PubMed


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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    • "KIAA0020 Broad Hematopoietic cells Fibroblasts HB-1 H/Y HLA-B * 44 Dolstra et al. 1999 [24] — Unknown Restricted B cell ALL, EBV-BLCLs ACC-1 HLA-A * 24 Akatsuka et al. 2003 [25] "
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    • "In brief, 106 target cells were resuspended in 2 ml virus supernatant and transferred to retronectin-coated dishes. After 24 h of incubation, cells were collected and incubated with fresh virus supernatant and used in CTL stimulation assays [29]. Release of IFNγ was determined by ELISA (Pierce Endogen, Rockford, IL). "
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