Graft γδ TCR Sequencing Identifies Public Clonotypes Associated with Hematopoietic Stem Cell Transplantation Efficacy in Acute Myeloid Leukemia Patients and Unravels Cytomegalovirus Impact on Repertoire Distribution

• DOI: 10.4049/jimmunol.1801448
• Publication Date: 2019-02-01T22:55:27Z
• Authors: Lucas C M Arruda; Ahmed Gaballa; Michael Uhlin
• Keywords: Cytomegalovirus

Abstract Although the impact of donor graft composition on clinical outcomes after hematopoietic stem cell transplantation (HSCT) has been studied, little is known about role intragraft γδ TCR repertoire following HSCT. Using a high-throughput sequencing platform, we sought to analyze γ-chain (TRG) T cells within grafts and address its potential response in corresponding patients. A total 20 peripheral blood were analyzed, donors classified as CMV+/−. The respective acute myeloid leukemia recipients followed for disease relapse graft-versus-host (aGvHD) development post-HSCT. In all samples, TRG showed reduced diversity displayed overrepresented clones. This was more prominent from CMV+ donors, which presented private repertoire, lower diversity, skewed distribution, usage V9-JP pairing. Grafts given nonrelapse patients public increased presence long sequence clonotypes. Variable-joining gene segment not associated with aGvHD development, but higher V2-JP1 pairing V4-J2/V5-J2/V8-JP2 observed Our work identified five one CDR3 (CATWDGPYYKKLF) CMV infection, addition 12 highly frequent sequences present exclusively findings show that, despite infection reshaping several are remission.