Disease relevance of HMHB1

• Interestingly, expression of the HB-1 gene was only observed in B-ALL cells and Epstein-Barr virus-transformed B cells [1].
• 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 [1].
• Avian leukosis virus (ALV) induces bursal lymphoma in chickens after proviral c-myc gene integration, while the HB-1 retrovirus carries a v-myc oncogene and also induces metastatic lymphoma [2].
• The morphologic and biochemical properties served to distinguish these organisms from similar bacteria implicated in human disease, such as Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Streptobacillus moniliformis, and HB-1 [3].
• We have determined the location of epitopes on the factor IX for three haemophilia B inhibitor antibodies (HB-1, HB-3, HB-7) and a monoclonal anti-factor IX inhibitory antibody (designated 65-10) [4].

High impact information on HMHB1

• This amino acid substitution is critical for recognition by HB-1-specific CTLs [1].
• 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 [1].
• From one of these HB-1-specific T-cell lines, we isolated a CD8+ CTL that produces interferon-gamma on stimulation with B-ALL tumor cells [5].
• In previous studies, we described HB-1 as a B-cell lineage-specific antigen that is recognized by donor-derived cytotoxic T lymphocytes (CTLs) on allogeneic B-ALL tumor cells [5].
• Mutual education between hematopoietic cells and bone marrow stromal cells through direct cell-to-cell contact: factors that determine the growth of bone marrow stroma-dependent leukemic (HB-1) cells [6].

Biological context of HMHB1

• These findings demonstrate that leukemia-associated mHag with a restricted tissue distribution, such as HB-1, elicit CTL reactivity in vivo [7].
• The HB-1 antigen is encoded by a locus of yet unknown function on chromosome 5q32 [8].

Anatomical context of HMHB1

• Here, we investigated the potential use of the HB-1 antigen as an autologous T-cell vaccine target [5].
• Characterization of the cells showed that HB-1 proliferated on hematopoietic supportive stromal cells (MS-10), but did not survive or proliferate on hematopoietic nonsupportive cells (MS-K) [6].
• A stroma-dependent cell line (HB-1) was established from myelogenous leukemic cells of CBA/N mouse [6].
• Moreover, the CTL clone does not lyse PHA-stimulated T cell blasts, monocytes, and fibroblasts, indicating that HB-1 is mainly expressed by transformed B cells [7].
• HB-1 is the first human mHag described that induces bi-directional allogeneic CTL responses that may contribute to a specific graft-versus-leukemia response following allogeneic stem cell transplantation [8].

Associations of HMHB1 with chemical compounds

• Using a set of synthetic structurally related peptide variants, we found that the H/Y substitution has a major impact on TCR recognition by CTL specific for either of the HB-1 allelic homologues [8].
• Digestion of plasma membranes with trypsin or Pronase resulted in a loss of activity of both HB1 and HB2 that was not influenced by prior treatment with neuraminidase, suggesting that sialic acid residues play no protective role against proteolytic cleavage of HDL receptor proteins [9].
• Proteins produced by HB1 cells under normal culture conditions included alpha-fetoprotein, cytokeratins 8 and 18, and lactate dehydrogenase (with an isozyme subunit composition similar to that of liver) [10].

Analytical, diagnostic and therapeutic context of HMHB1

• Generation of autologous cytotoxic and helper T-cell responses against the B-cell leukemia-associated antigen HB-1: relevance for precursor B-ALL-specific immunotherapy [5].
• Here, we report the identification of a B cell leukemia-associated mHag, HB-1, recognized by a CD8+ CTL clone derived from peripheral blood of an acute lymphoblastic B cell leukemia patient who has been treated by HLA-matched bone marrow transplantation [7].
• We have previously described the epitope mapping and functional neutralization of three factor IX inhibitors in hemophilia B (HB-1, 3, and 7) by synthetic peptides (13) [11].
• HB1 cells required fetal calf serum but grew well in culture (population doubling time of 2 days) and had an undifferentiated appearance under electron microscopy [10].

References