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 Blood, 1 May 2007, Vol. 109, No. 9, pp. 4089-4096.
Prepublished online as a Blood First Edition Paper on January 18, 2007; DOI 10.1182/blood-2006-08-043935.

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TRANSPLANTATION

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

Cornelis A. M. van Bergen1, Michel G. D. Kester1, Inge Jedema1, Mirjam H. M. Heemskerk1, Simone A. P. van Luxemburg-Heijs1, Freke M. Kloosterboer1, W. A. Erik Marijt1, Arnoud H. de Ru2, M. Ron Schaafsma3, Roel Willemze1, Peter A. van Veelen2, and J. H. Frederik Falkenburg1

1 Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, The Netherlands; 2 Department of Immunohematology and Blood Transfusion, Centre for Medical Systems Biology, Leiden University Medical Center, The Netherlands; 3 Medisch Spectrum Twente, Enschede, The Netherlands

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.


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