The PANE1 gene encodes a novel human minor histocompatibility antigen that is selectively expressed in B-lymphoid cells and B-CLL.
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.
Brickner
Anthony G
AG
Department of Medicine, Unviersity of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, PA, USA.
Evans
Anne M
AM
Mito
Jeffrey K
JK
Xuereb
Suzanne M
SM
Feng
Xin
X
Nishida
Tetsuya
T
Fairfull
Liane
L
Ferrell
Robert E
RE
Foon
Kenneth A
KA
Hunt
Donald F
DF
Shabanowitz
Jeffrey
J
Engelhard
Victor H
VH
Riddell
Stanley R
SR
Warren
Edus H
EH
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
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