1. Ex vivo detection of CD8 T cells specific for H-Y minor histocompatibility antigens in allogeneic hematopoietic stem cell transplant recipients.
- Author
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Nakamura, Ryotaro, La Rosa, Corinna, Tsai, Weimin, Lacey, Simon F., Srivastava, Tumul, Seidel, Aprille, Senitzer, David, Forman, Stephen J., and Diamond, Don J.
- Subjects
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CD8 antigen , *HEMATOPOIETIC stem cell transplantation , *T cells , *HISTOCOMPATIBILITY antigens , *GRAFT versus host disease , *GENE expression , *EPITOPES - Abstract
Immunologie 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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