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.
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 humanleukocyte 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.
Authors: Jeffrey S Miller; Edus H Warren; Marcel R M van den Brink; Jerome Ritz; Warren D Shlomchik; William J Murphy; A John Barrett; Hans Jochem Kolb; Sergio Giralt; Michael R Bishop; Bruce R Blazar; J H Frederik Falkenburg Journal: Biol Blood Marrow Transplant Date: 2010-02-10 Impact factor: 5.742
Authors: Persis P Wadia; Marc Coram; Randall J Armstrong; Michael Mindrinos; Atul J Butte; David B Miklos Journal: Blood Date: 2010-01-06 Impact factor: 22.113
Authors: Steven A McCarroll; James E Bradner; Hannu Turpeinen; Liisa Volin; Paul J Martin; Shannon D Chilewski; Joseph H Antin; Stephanie J Lee; Tapani Ruutu; Barry Storer; Edus H Warren; Bo Zhang; Lue Ping Zhao; David Ginsburg; Robert J Soiffer; Jukka Partanen; John A Hansen; Jerome Ritz; Aarno Palotie; David Altshuler Journal: Nat Genet Date: 2009-12 Impact factor: 38.330
Authors: N Santos; R Rodríguez-Romanos; J B Nieto; I Buño; C Vallejo; A Jiménez-Velasco; S Brunet; E Buces; J López-Jiménez; M González; C Ferrá; A Sampol; R de la Cámara; C Martínez; D Gallardo Journal: Bone Marrow Transplant Date: 2015-09-14 Impact factor: 5.483
Authors: Edus H Warren; Xinyi Cindy Zhang; Shuying Li; Wenhong Fan; Barry E Storer; Jason W Chien; Michael J Boeckh; Lue Ping Zhao; Paul J Martin; John A Hansen Journal: Blood Date: 2012-08-02 Impact factor: 22.113