that is selectively expressed in B-lymphoid cells and B-CLL The PANE1 gene encodes a novel human minor histocompatibility antigen

Abstract Minor histocompatibility antigens (mHAg) are peptides encoded by polymorphic genes that are presented by MHC molecules and recognized by T cells in recipients of allogeneic hematopoietic cell transplants. Here we report that an alternative transcript of the proliferation associated nuclear element 1 ( PANE1 ) gene encodes a novel HLA-A*0301-restricted mHAg that is selectively expressed in B-lymphoid cells. The antigenic peptide is entirely encoded within a unique exon not present in other PANE1 transcripts. Sequencing of PANE1 alleles in mHAg- positive and mHAg- negative cells demonstrates that differential T cell recognition is due to a single nucleotide polymorphism within the variant exon that replaces an arginine codon with a translation termination codon. The PANE1 transcript that encodes the mHAg is expressed at high levels in resting CD19 + B cells and B-lineage chronic lymphocytic leukemia (B-CLL) cells, and at significantly lower levels in activated B cells. Activation of B-CLL cells through CD40L stimulation decreases expression of the mHAg-encoding

[1]  C. Mackay,et al.  BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders. , 2005, Human pathology.

[2]  M. Kojima,et al.  Expression of BAFF-R (BR3) in normal and neoplastic lymphoid tissues characterized with a newly developed monoclonal antibody , 2005, Virchows Archiv.

[3]  Geoffrey B. Nilsen,et al.  Whole-Genome Patterns of Common DNA Variation in Three Human Populations , 2005, Science.

[4]  M. Leppert,et al.  Allogeneic Hematopoietic Cell Transplantation for Metastatic Renal Cell Carcinoma after Nonmyeloablative Conditioning , 2004, Clinical Cancer Research.

[5]  J. Falkenburg,et al.  Minor histocompatibility antigens as targets of cellular immunotherapy in leukaemia. , 2004, Best practice & research. Clinical haematology.

[6]  L. Hennighausen,et al.  The proliferation associated nuclear element (PANE1) is conserved between mammals and fish and preferentially expressed in activated lymphoid cells. , 2004, Gene expression patterns : GEP.

[7]  S. Riddell,et al.  Molecules and mechanisms of the graft-versus-leukaemia effect , 2004, Nature Reviews Cancer.

[8]  N. Chao Minors come of age: Minor histocompatibility antigens and graft-versus-host disease. , 2004, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[9]  C. Obuse,et al.  Proteomics analysis of the centromere complex from HeLa interphase cells: UV‐damaged DNA binding protein 1 (DDB‐1) is a component of the CEN‐complex, while BMI‐1 is transiently co‐localized with the centromeric region in interphase , 2004, Genes to cells : devoted to molecular & cellular mechanisms.

[10]  F. Ajchenbaum‐Cymbalista,et al.  Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway. , 2004, Blood.

[11]  Ming-Tseh Lin,et al.  Disparity for a newly identified minor histocompatibility antigen, HA‐8, correlates with acute graft‐versus‐host disease after haematopoietic stem cell transplantation from an HLA‐identical sibling , 2003, British journal of haematology.

[12]  L. Hennighausen,et al.  Identification of genes differentially expressed in mouse mammary epithelium transformed by an activated β-catenin , 2003, Oncogene.

[13]  J. Shabanowitz,et al.  The minor Histocompatibility antigen HA-3 arises from differential proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein , 2003 .

[14]  T. Naoe,et al.  Identification of a Polymorphic Gene, BCL2A1, Encoding Two Novel Hematopoietic Lineage-specific Minor Histocompatibility Antigens , 2003, The Journal of experimental medicine.

[15]  E. Warren,et al.  A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion , 2003, The Journal of experimental medicine.

[16]  Serge Picard,et al.  The model B6dom1 minor histocompatibility antigen is encoded by a mouse homolog of the yeast STT3 gene , 2002, Immunogenetics.

[17]  A. Balas,et al.  Bi‐directional allelic recognition of the human minor histocompatibility antigen HB‐1 by cytotoxic T lymphocytes , 2002, European journal of immunology.

[18]  Kathryn E. Hentges,et al.  Tnfrsf13c (Baffr) is mis-expressed in tumors with murine leukemia virus insertions at Lvis22. , 2002, Genomics.

[19]  T. Schumacher,et al.  In situ dissection of the graft-versus-host activities of cytotoxic T cells specific for minor histocompatibility antigens , 2002, Nature Medicine.

[20]  M. Scott,et al.  An Essential Role for BAFF in the Normal Development of B Cells Through a BCMA-Independent Pathway , 2001, Science.

[21]  J. Tschopp,et al.  BAFF-R, a Newly Identified TNF Receptor That Specifically Interacts with BAFF , 2001, Science.

[22]  J. Shabanowitz,et al.  The Immunogenicity of a New Human Minor Histocompatibility Antigen Results from Differential Antigen Processing , 2001, The Journal of experimental medicine.

[23]  J. Shabanowitz,et al.  Subfemtomole MS and MS/MS peptide sequence analysis using nano-HPLC micro-ESI fourier transform ion cyclotron resonance mass spectrometry. , 2000, Analytical chemistry.

[24]  J. Shabanowitz,et al.  Cutting edge: the HLA-A*0101-restricted HY minor histocompatibility antigen originates from DFFRY and contains a cysteinylated cysteine residue as identified by a novel mass spectrometric technique. , 1999, Journal of immunology.

[25]  C. Figdor,et al.  A Human Minor Histocompatibility Antigen Specific for B Cell Acute Lymphoblastic Leukemia , 1999, The Journal of experimental medicine.

[26]  S. Riddell,et al.  In vivo migration and function of transferred HIV-1-specific cytotoxic T cells , 1999, Nature Medicine.

[27]  N. Shastri,et al.  The molecular and functional characterization of a dominant minor H antigen, H60. , 1998, Journal of immunology.

[28]  J. Shabanowitz,et al.  The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymorphism. , 1998, Science.

[29]  J. Gribben,et al.  CD40-activated human B cells: an alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy. , 1997, The Journal of clinical investigation.

[30]  A. Agulnik,et al.  The HLA-A*0201-restricted H-Y antigen contains a posttranslationally modified cysteine that significantly affects T cell recognition. , 1997, Immunity.

[31]  P. Koopman,et al.  An H–YDb epitope is encoded by a novel mouse Y chromosome gene , 1996, Nature Genetics.

[32]  A. Agulnik,et al.  Human H-Y: a male-specific histocompatibility antigen derived from the SMCY protein. , 1995, Science.

[33]  F Koning,et al.  Identification of a graft versus host disease-associated human minor histocompatibility antigen. , 1995, Science.

[34]  R. Henderson,et al.  Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. , 1994, Science.

[35]  A. Bakker,et al.  Tissue distribution of human minor histocompatibility antigens. Ubiquitous versus restricted tissue distribution indicates heterogeneity among human cytotoxic T lymphocyte-defined non-MHC antigens. , 1992, Journal of immunology.

[36]  W. Britt,et al.  Class I MHC-restricted cytotoxic T lymphocyte recognition of cells infected with human cytomegalovirus does not require endogenous viral gene expression. , 1991, Journal of immunology.

[37]  J. Jorgenson,et al.  Quantitative analysis of individual neurons by open tubular liquid chromatography with voltammetric detection. , 1989, Analytical chemistry.

[38]  M. Epstein,et al.  T-cell-mediated regression of "spontaneous" and of Epstein-Barr virus-induced B-cell transformation in vitro: studies with cyclosporin A. , 1984, Cellular immunology.

[39]  P. Cresswell,et al.  Monoclonal antibody to HLA-A3. , 1982, Hybridoma.