title: Ex vivo detection of CD8 T cells specific for H-Y minor histocompatibility antigens in allogeneic hematopoietic stem cell transplant recipients.
abstract: Immunologic disparities between minor histocompatibility antigen (mHAg) genes on Y (H-Y) and X (H-X) chromosomes contribute to graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects observed in male recipients of a female donor (FtoM) hematopoietic stem cell transplant (HCT). Using in silico prediction tools, a panel of HLA-A0201 restricted H-Y peptides was synthesized. Expression of CD137 was monitored on CD8(+) T cells after brief stimulation with the H-Y peptides in FtoM HLA-A0201 HCT recipients (N=29), and control groups (HLA-A0201 MtoM [N=18], non-HLA-A0201 FtoM [N=14], and HLA-A0201 female volunteers [N=25]). Specific H-Y responses were significantly greater in HLA-A0201 FtoM than controls. CD8(+) T-cell responses to novel H-Y epitopes were shared among multiple patients, showing marked CD45RA(+)CD27 cytolytic effector profiles. These data represent a proof of concept for our in silico/ex vivo CD8(+) T-cell based approach of prediction and validation of H-Y mHAgs in HCT recipients, which may facilitate prospective studies to identify targets/biomarkers of GVHD/GVL.
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, United States. Electronic address: rnakamura@coh.org.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Nakamura
authors.affiliation: Division of Translational Vaccine Research, City of Hope Comprehensive Cancer Center and Beckman Research Institute of the City of Hope, Duarte, CA, United States.
authors.forename: Corinna
authors.initials: C
authors.lastname: La Rosa
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, United States.
authors.forename: Weimin
authors.initials: W
authors.lastname: Tsai
authors.affiliation: Division of Translational Vaccine Research, City of Hope Comprehensive Cancer Center and Beckman Research Institute of the City of Hope, Duarte, CA, United States.
authors.forename: Simon F
authors.initials: SF
authors.lastname: Lacey
authors.affiliation: Division of Translational Vaccine Research, City of Hope Comprehensive Cancer Center and Beckman Research Institute of the City of Hope, Duarte, CA, United States.
authors.forename: Tumul
authors.initials: T
authors.lastname: Srivastava
authors.affiliation: Division of Translational Vaccine Research, City of Hope Comprehensive Cancer Center and Beckman Research Institute of the City of Hope, Duarte, CA, United States.
authors.forename: Aprille
authors.initials: A
authors.lastname: Seidel
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, United States.
authors.forename: David
authors.initials: D
authors.lastname: Senitzer
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, United States.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.affiliation: Division of Translational Vaccine Research, City of Hope Comprehensive Cancer Center and Beckman Research Institute of the City of Hope, Duarte, CA, United States.
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D020544:Graft vs Leukemia Effect / Q000276:immunology; D006182:H-Y Antigen / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D066027:Transplant Recipients; D014184:Transplantation, Homologous; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000096:biosynthesis / Q000276:immunology; D055815:Young Adult
chemical_list: D006182:H-Y Antigen; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens
keywords: CD137 assay; CD8 T cell; GVHD; GVL; H-Y minor histocompatibility antigen; Hematopoietic stem cell transplant