PMID- 16391015 OWN - NLM STAT- MEDLINE DCOM- 20060524 LR - 20210526 IS - 0006-4971 (Print) IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 107 IP - 9 DP - 2006 May 1 TI - The PANE1 gene encodes a novel human minor histocompatibility antigen that is selectively expressed in B-lymphoid cells and B-CLL. PG - 3779-86 AB - 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. FAU - Brickner, Anthony G AU - Brickner AG AD - Department of Medicine, Unviersity of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, PA, USA. FAU - Evans, Anne M AU - Evans AM FAU - Mito, Jeffrey K AU - Mito JK FAU - Xuereb, Suzanne M AU - Xuereb SM FAU - Feng, Xin AU - Feng X FAU - Nishida, Tetsuya AU - Nishida T FAU - Fairfull, Liane AU - Fairfull L FAU - Ferrell, Robert E AU - Ferrell RE FAU - Foon, Kenneth A AU - Foon KA FAU - Hunt, Donald F AU - Hunt DF FAU - Shabanowitz, Jeffrey AU - Shabanowitz J FAU - Engelhard, Victor H AU - Engelhard VH FAU - Riddell, Stanley R AU - Riddell SR FAU - Warren, Edus H AU - Warren EH LA - eng GR - CA18029/CA/NCI NIH HHS/United States GR - AI339933/AI/NIAID NIH HHS/United States GR - AI44134/AI/NIAID NIH HHS/United States GR - AI20963/AI/NIAID NIH HHS/United States GR - CA106512/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060103 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD19) RN - 0 (CENPM protein, human) RN - 0 (Cell Cycle Proteins) RN - 0 (Epitopes) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A*03:01 antigen) RN - 0 (HLA-A3 Antigen) RN - 0 (Minor Histocompatibility Antigens) RN - 0 (Nuclear Proteins) RN - 9007-49-2 (DNA) SB - IM MH - Alternative Splicing MH - Amino Acid Sequence MH - Antigens, CD19/metabolism MH - B-Lymphocytes/*immunology MH - Base Sequence MH - Cell Cycle Proteins MH - DNA/genetics MH - Epitopes/chemistry MH - Gene Expression MH - HLA-A Antigens/genetics MH - HLA-A3 Antigen MH - Humans MH - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics/*immunology MH - Lymphocyte Activation MH - Minor Histocompatibility Antigens/chemistry/*genetics MH - *Minor Histocompatibility Loci MH - Molecular Sequence Data MH - Nuclear Proteins/chemistry/*genetics/*immunology MH - Spectrometry, Mass, Electrospray Ionization MH - T-Lymphocytes, Cytotoxic/immunology PMC - PMC1895781 EDAT- 2006/01/05 09:00 MHDA- 2006/05/25 09:00 PMCR- 2007/05/01 CRDT- 2006/01/05 09:00 PHST- 2006/01/05 09:00 [pubmed] PHST- 2006/05/25 09:00 [medline] PHST- 2006/01/05 09:00 [entrez] PHST- 2007/05/01 00:00 [pmc-release] AID - S0006-4971(20)65568-9 [pii] AID - 3779 [pii] AID - 10.1182/blood-2005-08-3501 [doi] PST - ppublish SO - Blood. 2006 May 1;107(9):3779-86. doi: 10.1182/blood-2005-08-3501. Epub 2006 Jan 3.