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Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen
- Source :
- Blood. 110:1055-1063
- Publication Year :
- 2007
- Publisher :
- American Society of Hematology, 2007.
-
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)/γcnull 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.
- Subjects :
- DNA, Complementary
Immunology
Epitopes, T-Lymphocyte
Mice, SCID
Human leukocyte antigen
Biology
Polymorphism, Single Nucleotide
Biochemistry
Epitope
HLA-B44 Antigen
Minor Histocompatibility Antigens
Mice
Antigen
Mice, Inbred NOD
Cell Line, Tumor
Minor histocompatibility antigen
Animals
Humans
Cytotoxic T cell
Myeloid leukemia
Cell Biology
Hematology
Molecular biology
Alternative Splicing
Haematopoiesis
CTL
HLA-B Antigens
Leukemia, Myeloid
Neoplastic Stem Cells
Immunotherapy
RNA Splice Sites
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 110
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....74f0bf82aa9e7ca143c05e6ccfd99da2