title: 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.affiliation: Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. c.a.m.van_bergen@lumc.nl
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: van Bergen
authors.forename: Michel G D
authors.initials: MG
authors.lastname: Kester
authors.forename: Inge
authors.initials: I
authors.lastname: Jedema
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
authors.forename: Simone A P
authors.initials: SA
authors.lastname: van Luxemburg-Heijs
authors.forename: Freke M
authors.initials: FM
authors.lastname: Kloosterboer
authors.forename: W A Erik
authors.initials: WA
authors.lastname: Marijt
authors.forename: Arnoud H
authors.initials: AH
authors.lastname: de Ru
authors.forename: M Ron
authors.initials: MR
authors.lastname: Schaafsma
authors.forename: Roel
authors.initials: R
authors.lastname: Willemze
authors.forename: Peter A
authors.initials: PA
authors.lastname: van Veelen
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
mesh_terms: D000251:Adenosine Triphosphatases / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000276:immunology; D017710:Lymphocyte Transfusion; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D018832:Molecular Chaperones / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D009928:Organ Specificity / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D012074:Remission Induction; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D018183:Transplantation Chimera / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015778:Minor Histocompatibility Antigens; D018832:Molecular Chaperones; D010455:Peptides; D000251:Adenosine Triphosphatases; C486741:TOR3A protein, human