PMID- 17409267
OWN - NLM
STAT- MEDLINE
DCOM- 20070921
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 110
IP  - 3
DP  - 2007 Aug 1
TI  - Alternative splicing due to an intronic SNP in HMSD generates a novel minor 
      histocompatibility antigen.
PG  - 1055-63
AB  - Here we report the identification of a novel human leukocyte antigen 
      (HLA)-B44-restricted minor histocompatibility antigen (mHA) with expression 
      limited to hematopoietic cells. cDNA expression cloning studies demonstrated that 
      the cytotoxic T lymphocyte (CTL) epitope of interest was encoded by a novel 
      allelic splice variant of HMSD, hereafter designated as HMSD-v. The 
      immunogenicity of the epitope was generated by differential protein expression 
      due to alternative splicing, which was completely controlled by 1 intronic 
      single-nucleotide polymorphism located in the consensus 5' splice site adjacent 
      to an exon. Both HMSD-v and HMSD transcripts were selectively expressed at higher 
      levels in mature dendritic cells and primary leukemia cells, especially those of 
      myeloid lineage. Engraftment of mHA(+) myeloid leukemia stem cells in nonobese 
      diabetic/severe combined immunodeficient (NOD/SCID)/gammac(null) mice was 
      completely inhibited by in vitro preincubation with the mHA-specific CTL clone, 
      suggesting that this mHA is expressed on leukemic stem cells. The patient from 
      whom the CTL clone was isolated demonstrated a significant increase of the 
      mHA-specific T cells in posttransplantation peripheral blood, whereas 
      mHA-specific T cells were undetectable in pretransplantation peripheral blood and 
      in peripheral blood from his donor. These findings suggest that the 
      HMSD-v-encoded mHA (designated ACC-6) could serve as a target antigen for 
      immunotherapy against hematologic malignancies.
FAU - Kawase, Takakazu
AU  - Kawase T
AD  - Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, 
      Chikusa-ku, Nagoya 464-8681, Japan.
FAU - Akatsuka, Yoshiki
AU  - Akatsuka Y
FAU - Torikai, Hiroki
AU  - Torikai H
FAU - Morishima, Satoko
AU  - Morishima S
FAU - Oka, Akira
AU  - Oka A
FAU - Tsujimura, Akane
AU  - Tsujimura A
FAU - Miyazaki, Mikinori
AU  - Miyazaki M
FAU - Tsujimura, Kunio
AU  - Tsujimura K
FAU - Miyamura, Koichi
AU  - Miyamura K
FAU - Ogawa, Seishi
AU  - Ogawa S
FAU - Inoko, Hidetoshi
AU  - Inoko H
FAU - Morishima, Yasuo
AU  - Morishima Y
FAU - Kodera, Yoshihisa
AU  - Kodera Y
FAU - Kuzushima, Kiyotaka
AU  - Kuzushima K
FAU - Takahashi, Toshitada
AU  - Takahashi T
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070404
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA, Complementary)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B44 Antigen)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (RNA Splice Sites)
SB  - IM
MH  - Alternative Splicing/*genetics/immunology
MH  - Animals
MH  - Cell Line, Tumor
MH  - DNA, Complementary/genetics/immunology
MH  - Epitopes, T-Lymphocyte/*genetics/immunology
MH  - HLA-B Antigens/genetics/immunology
MH  - HLA-B44 Antigen
MH  - Humans
MH  - Immunotherapy
MH  - Leukemia, Myeloid/*genetics/immunology/therapy
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Minor Histocompatibility Antigens/*genetics/immunology
MH  - Neoplastic Stem Cells
MH  - *Polymorphism, Single Nucleotide
MH  - RNA Splice Sites
MH  - T-Lymphocytes, Cytotoxic/immunology
EDAT- 2007/04/06 09:00
MHDA- 2007/09/22 09:00
CRDT- 2007/04/06 09:00
PHST- 2007/04/06 09:00 [pubmed]
PHST- 2007/09/22 09:00 [medline]
PHST- 2007/04/06 09:00 [entrez]
AID - S0006-4971(20)49564-3 [pii]
AID - 10.1182/blood-2007-02-075911 [doi]
PST - ppublish
SO  - Blood. 2007 Aug 1;110(3):1055-63. doi: 10.1182/blood-2007-02-075911. Epub 2007 
      Apr 4.