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.