Epitopes described in "A single minor histocompatibility antigen encoded by UGT2B17 and presented by human leukocyte antigen-A*2902 and -B*4403."

Article Authors:Seitaro Terakura; Makoto Murata; Edus H Warren; Alessandro Sette; John Sidney; Tomoki Naoe; Stanley R Riddell
Article Title:A single minor histocompatibility antigen encoded by UGT2B17 and presented by human leukocyte antigen-A*2902 and -B*4403.
Reference Detail
Reference ID:1020267
Abstract:BACKGROUND: T-cell responses to minor histocompatibility antigens are mediators of graft-versus-host disease and organ graft rejection. We previously identified a human minor histocompatibility antigen that is recognized by CD8 cytotoxic T lymphocytes (CTLs) and encoded by the UDP glycosyltransferase 2 family, polypeptide B17 (UGT2B17) gene, which is highly expressed in the liver, colon, and small intestine. The UGT2B17 is presented by human leukocyte antigen (HLA)-A*2902, and the immunogenicity of this minor histocompatibility antigen results from differential protein expression in donor and recipient cells as a consequence of a UGT2B17 gene deletion. METHODS: An HLA-B*4403-restricted CD8 CTL clone was isolated from the same hematopoietic stem cell transplant recipient that exhibited an HLA-A*2902-restricted UGT2B17-specific response. The minor histocompatibility antigen recognized by the HLA-B*4403-restricted clone was identified, and the ability of the peptide to be presented by HLA-B*4402 was examined. RESULTS: The HLA-B*4403-restricted CTL clone recognized a peptide encoded by UGT2B17, which is identical to the peptide presented by HLA-A*2902. Peptide binding assays revealed this UGT2B17 peptide binds with comparable affinity to HLA-B*4402 as to HLA-B*4403. This patient had acute graft-versus-host disease involving liver and gastrointestinal tract, suggesting the T-cell response directed against UGT2B17 is involved in graft-versus-host disease. CONCLUSIONS: A single peptide encoded by UGT2B17 can be presented by HLA-A*2902, B*4402 and B*4403, and may serve as an immunodominant minor histocompatibility antigen in individuals with these HLA alleles that undergo transplantation of stem cells or organ grafts from UGT2B17 disparate donors.
Affiliations:Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Reference Type:Literature
PubMed ID:17496542
Journal Volume:83
Article Pages:1242-8
Journal ISSN:0041-1337
Article Chemical List:Epitopes;HLA-A Antigens;HLA-A*29:02 antigen;HLA-B Antigens;HLA-B*44:03 antigen;HLA-B44 Antigen;Histocompatibility Antigens;Minor Histocompatibility Antigens;Peptide Fragments;Glucuronosyltransferase;UGT2B17 protein, human
Article MeSH List:Amino Acid Sequence; Animals; Base Sequence; COS Cells; Cells, Cultured; Cercopithecus aethiops; Clone Cells; Epitopes(genetics); Gastrointestinal Diseases(immunology); Glucuronosyltransferase(chemistry; immunology); Graft vs Host Disease(immunology); HLA-A Antigens(immunology); HLA-B Antigens(immunology); HLA-B44 Antigen; Hematopoietic Stem Cell Transplantation(adverse effects); Histocompatibility Antigens(immunology); Humans; Liver Diseases(immunology); Minor Histocompatibility Antigens(immunology); Molecular Sequence Data; Peptide Fragments(genetics; immunology); T-Lymphocytes, Cytotoxic(immunology)
Curation Last Updated:2014-10-03 22:10:29