Epitopes described in "Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen."

Article Authors:Takakazu Kawase; Yoshiki Akatsuka; Hiroki Torikai; Satoko Morishima; Akira Oka; Akane Tsujimura; Mikinori Miyazaki; Kunio Tsujimura; Koichi Miyamura; Seishi Ogawa; Hidetoshi Inoko; Yasuo Morishima; Yoshihisa Kodera; Kiyotaka Kuzushima; Toshitada Takahashi
Article Title:Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen.
Reference Detail
Reference ID:1020268
Abstract: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.
Affiliations:Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Reference Type:Literature
PubMed ID:17409267
Journal Volume:110
Article Pages:1055-63
Journal ISSN:1528-0020
Article Chemical List:DNA, Complementary;Epitopes, T-Lymphocyte;HLA-B Antigens;HLA-B44 Antigen;Minor Histocompatibility Antigens;RNA Splice Sites
Article MeSH List:Alternative Splicing(genetics; immunology); Animals; Cell Line, Tumor; DNA, Complementary(genetics; immunology); Epitopes, T-Lymphocyte(genetics; immunology); HLA-B Antigens(genetics; immunology); HLA-B44 Antigen; Humans; Immunotherapy; Leukemia, Myeloid(genetics; immunology; therapy); Mice; Mice, Inbred NOD; Mice, SCID; Minor Histocompatibility Antigens(genetics; immunology); Neoplastic Stem Cells; Polymorphism, Single Nucleotide; RNA Splice Sites; T-Lymphocytes, Cytotoxic(immunology)
Curation Last Updated:2014-10-03 22:10:29