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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3779-3786.
Prepublished online as a Blood First Edition Paper on January 3, 2006; DOI 10.1182/blood-2005-08-3501.
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TRANSPLANTATION
The PANE1 gene encodes a novel human minor histocompatibility antigen that is selectively expressed in B-lymphoid cells and B-CLL
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, and
Edus H. Warren
From the University of Pittsburgh Cancer Institute and Departments of Medicine and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh; Department of Microbiology and Carter Immunology Center, and Departments of Chemistry and Pathology, University of Virginia, Charlottesville, VA; Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine, University of Washington, Seattle, WA.
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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