A single minor histocompatibility antigen encoded by UGT2B17 and presented by human leukocyte antigen-A*2902 and -B*4403.
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.
Terakura
Seitaro
S
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Murata
Makoto
M
Warren
Edus H
EH
Sette
Alessandro
A
Sidney
John
J
Naoe
Tomoki
T
Riddell
Stanley R
SR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002999:Clone Cells; D000939:Epitopes / Q000235:genetics; D005767:Gastrointestinal Diseases / Q000276:immunology; D014453:Glucuronosyltransferase / Q000737:chemistry / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D059948:HLA-B44 Antigen; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D008107:Liver Diseases / Q000276:immunology; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000939:Epitopes; D015234:HLA-A Antigens; C520711:HLA-A*29:02 antigen; D015235:HLA-B Antigens; C495439:HLA-B*44:03 antigen; D059948:HLA-B44 Antigen; D006649:Histocompatibility Antigens; D015778:Minor Histocompatibility Antigens; D010446:Peptide Fragments; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human