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| Article Authors: | Anthony G Brickner; Anne M Evans; Jeffrey K Mito; Suzanne M Xuereb; Xin Feng; Tetsuya Nishida; Liane Fairfull; Robert E Ferrell; Kenneth A Foon; Donald F Hunt; Jeffrey Shabanowitz; Victor H Engelhard; Stanley R Riddell; Edus H Warren |
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| Article Title: | The PANE1 gene encodes a novel human minor histocompatibility antigen that is selectively expressed in B-lymphoid cells and B-CLL. |
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| Reference ID: | 1020273 |
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| Abstract: | Minor histocompatibility antigens (mHAg's) are peptides encoded by polymorphic genes that are presented by major histocompatibility complex (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 human leukocyte antigen (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 CD40 ligand (CD40L) stimulation decreases expression of the mHAg-encoding PANE1 transcript and reciprocally increases expression of PANE1 transcripts lacking the mHAg-encoding exon. These studies suggest distinct roles for different PANE1 isoforms in resting compared with activated CD19(+) cells, and identify PANE1 as a potential therapeutic target in B-CLL. |
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| Affiliations: | Department of Medicine, Unviersity of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, PA, USA. |
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| Date: | 2006 |
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| Reference Type: | Literature |
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| PubMed ID: | 16391015 |
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| Journal: | Blood |
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| Journal Volume: | 107 |
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| Article Pages: | 3779-86 |
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| Journal ISSN: | 1528-0020 |
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| Article Chemical List: | Antigens, CD19;Epitopes;HLA-A Antigens;HLA-A*03:01 antigen;Minor Histocompatibility Antigens;Nuclear Proteins;proliferation associated nuclear element protein 1, human;DNA |
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| Article MeSH List: | Alternative Splicing; Amino Acid Sequence; Antigens, CD19(metabolism); B-Lymphocytes(immunology); Base Sequence; DNA(genetics); Epitopes(chemistry); Gene Expression; HLA-A Antigens(genetics); Humans; Leukemia, Lymphocytic, Chronic, B-Cell(genetics; immunology); Lymphocyte Activation; Minor Histocompatibility Antigens(chemistry; genetics); Minor Histocompatibility Loci; Molecular Sequence Data; Nuclear Proteins(chemistry; genetics; immunology); Spectrometry, Mass, Electrospray Ionization; T-Lymphocytes, Cytotoxic(immunology) |
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| Curation Last Updated: | 2013-05-28 22:15:50 |
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