title: The PANE1 gene encodes a novel human minor histocompatibility antigen that is selectively expressed in B-lymphoid cells and B-CLL.
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.
authors.affiliation: Department of Medicine, Unviersity of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, PA, USA.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Brickner
authors.forename: Anne M
authors.initials: AM
authors.lastname: Evans
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Mito
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Xuereb
authors.forename: Xin
authors.initials: X
authors.lastname: Feng
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nishida
authors.forename: Liane
authors.initials: L
authors.lastname: Fairfull
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Foon
authors.forename: Donald F
authors.initials: DF
authors.lastname: Hunt
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shabanowitz
authors.forename: Victor H
authors.initials: VH
authors.lastname: Engelhard
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D018797:Cell Cycle Proteins; D004247:DNA / Q000235:genetics; D000939:Epitopes / Q000737:chemistry; D015870:Gene Expression; D015234:HLA-A Antigens / Q000235:genetics; D015791:HLA-A3 Antigen; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology*; D008213:Lymphocyte Activation; D015778:Minor Histocompatibility Antigens / Q000737:chemistry / Q000235:genetics*; D008912:Minor Histocompatibility Loci; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D018941:Antigens, CD19; C495719:CENPM protein, human; D018797:Cell Cycle Proteins; D000939:Epitopes; D015234:HLA-A Antigens; C442141:HLA-A*03:01 antigen; D015791:HLA-A3 Antigen; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D004247:DNA