Multiple myeloma-reactive T cells recognize an activation-induced minor histocompatibility antigen encoded by the ATP-dependent interferon-responsive (ADIR) gene.
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.
van Bergen
Cornelis A M
CA
Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. c.a.m.van_bergen@lumc.nl
Kester
Michel G D
MG
Jedema
Inge
I
Heemskerk
Mirjam H M
MH
van Luxemburg-Heijs
Simone A P
SA
Kloosterboer
Freke M
FM
Marijt
W A Erik
WA
de Ru
Arnoud H
AH
Schaafsma
M Ron
MR
Willemze
Roel
R
van Veelen
Peter A
PA
Falkenburg
J H Frederik
JH
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*
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015778:Minor Histocompatibility Antigens; D018832:Molecular Chaperones; D010455:Peptides; D000251:Adenosine Triphosphatases; C486741:TOR3A protein, human