1. T-cell receptor repertoire of cytomegalovirus-specific cytotoxic T-cells after allogeneic stem cell transplantation
- Author
-
Fumi Misumi, Tatsuya Konishi, Kota Yoshifuji, Takeshi Kobayashi, Takashi Toya, Atsushi Marumo, Kyoko Inamoto, Yuya Kishida, Ryuji Suzuki, Kazutaka Kitaura, Hiroto Adachi, Akihito Nagata, Ryosuke Konuma, Yuho Najima, Yuma Noguchi, Noriko Doki, Aiko Igarashi, Kazuteru Ohashi, Junichi Mukae, Yuki Otsuka, Yuta Yamada, Takeshi Nagamatsu, Yujiro Nakajima, Ayumi Taguchi, Kazuhiko Kakihana, and Atsushi Wada
- Subjects
0301 basic medicine ,Adult ,Male ,Science ,Immunology ,Receptors, Antigen, T-Cell ,Cytomegalovirus ,chemical and pharmacologic phenomena ,T-Cell Antigen Receptor Specificity ,Biology ,Article ,Immunophenotyping ,Clonal Evolution ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Medical research ,Antigen ,Transplant immunology ,Transplantation Immunology ,Cytotoxic T cell ,Humans ,Transplantation, Homologous ,Aged ,Multidisciplinary ,T-cell receptor ,Hematopoietic Stem Cell Transplantation ,virus diseases ,hemic and immune systems ,Middle Aged ,Acquired immune system ,Transplantation ,030104 developmental biology ,Viral infection ,Cytomegalovirus Infections ,Medicine ,Female ,Disease Susceptibility ,Stem cell ,CD8 ,Biomarkers ,030215 immunology ,T-Lymphocytes, Cytotoxic - Abstract
Cytomegalovirus (CMV) infection is a major complication during allogeneic stem cell transplantation (allo-SCT). However, mechanisms of adaptive immunity that drive this remain unclear. To define early immunological responses to CMV after transplantation, we using next-generation sequencing to examine the repertoire of T-cell receptors in CD8+/CMV pp65 tetramer+ cells (CMV-CTLs) in peripheral blood samples obtained from 16 allo-SCT recipients with HLA-A*24:02 at the time of CMV reactivation. In most patients, TCR beta repertoire of CMV-CTLs was highly skewed (median Inverse Simpson’s index: 1.595) and, 15 of 16 patients shared at least one TCR-beta clonotype with ≥ 2 patients. The shared TCRs were dominant in 12 patients and, two clonotypes were shared by about half of the patients. Similarity analysis showed that CDR3 sequences of shared TCRs were more similar than unshared TCRs. TCR beta repertoires of CMV-CTLs in 12 patients were also analyzed after 2–4 weeks to characterize the short-term dynamics of TCR repertoires. In ten patients, we observed persistence of prevailing clones. In the other two patients, TCR repertoires became more diverse, major clones declined, and new private clones subsequently emerged. These results provided the substantive clue to understand the immunological behavior against CMV reactivation after allo-SCT.
- Published
- 2020