Multiple myeloma-reactive T cells recognize an activation-induced minor histocompatibility antigen encoded by the ATP-dependent interferon-responsive (ADIR) gene.

Abstract

Minor histocompatibility antigens (mHags) play an important role in both graft-versus-tumor effects and graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. We applied biochemical techniques and mass spectrometry to identify the peptide recognized by a dominant tumor-reactive donor T-cell reactivity isolated from a patient with relapsed multiple myeloma who underwent transplantation and entered complete remission after donor lymphocyte infusion. A frequently occurring single nucleotide polymorphism in the human ATP-dependent interferon-responsive (ADIR) gene was found to encode the epitope we designated LB-ADIR-1F. Although gene expression could be found in cells from hematopoietic as well as nonhematopoietic tissues, the patient suffered from only mild acute GVHD despite high percentages of circulating LB-ADIR-1F-specific T cells. Differential recognition of nonhematopoietic cell types and resting hematopoietic cells as compared with activated B cells, T cells, and tumor cells was demonstrated, illustrating variable LB-ADIR-1F expression depending on the cellular activation state. In conclusion, the novel mHag LB-ADIR-1F may be a suitable target for cellular immunotherapy when applied under controlled circumstances.

• Authors: Cornelis A M van Bergen, Michel G D Kester, Inge Jedema, Mirjam H M Heemskerk, Simone A P van Luxemburg-Heijs, Freke M Kloosterboer, W A Erik Marijt, Arnoud H de Ru, M Ron Schaafsma, Roel Willemze, Peter A van Veelen, J H Frederik Falkenburg
• Journal: Blood (Blood) Vol. 109 Issue 9 Pg. 4089-96 (May 01 2007) ISSN: 0006-4971 [Print] United States
• PMID: 17234742 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Epitopes, T-Lymphocyte
• Minor Histocompatibility Antigens
• Molecular Chaperones
• Peptides
• Adenosine Triphosphatases
• TOR3A protein, human

Topics

• Adenosine Triphosphatases (immunology)
• Antigens, Neoplasm (immunology)
• Epitope Mapping
• Epitopes, T-Lymphocyte (immunology)
• Female
• Gene Expression Regulation
• Graft vs Host Disease (immunology)
• Graft vs Tumor Effect (immunology)
• Hematopoietic Stem Cells (immunology)
• Humans
• Immunotherapy
• Lymphocyte Activation (immunology)
• Lymphocyte Transfusion
• Male
• Minor Histocompatibility Antigens (immunology)
• Molecular Chaperones (immunology)
• Multiple Myeloma (immunology, therapy)
• Organ Specificity (immunology)
• Peptides (immunology)
• Remission Induction
• Stem Cell Transplantation
• T-Lymphocytes (immunology)
• Transplantation Chimera (immunology)