T-cell receptor repertoire of cytomegalovirus-specific cytotoxic T-cells after allogeneic stem cell transplantation

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.

Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT

“…To document the impact of allogeneic HLA class I molecules on the modulation of KIR2DL3 + T cell function and in absence of well-established leukemia model, we focused our investigations on HLA-A2-pp65 specific T lymphocytes. Indeed, KIR expression has been previously documented on these cells in allogeneic HSCT patients 31 , 42 . HLA-C*04:01 encoded molecule belongs to C2 group of KIR ligands.…”

Attenuated humoral response against SARS‐CoV‐2 mRNA vaccination in allogeneic stem cell transplantation recipients

“…These results might reflect impaired immunity in the recipients. However, CMV reactivation is associated with modified immunity [25][26][27][28] and variable infections. [29][30][31] In addition,…”

“…These results might reflect impaired immunity in the recipients. However, CMV reactivation is associated with modified immunity 25–28 and variable infections 29–31 . In addition, CMV reactivation has been reported to be associated with a poor response after vaccination against hepatitis B virus in SCT recipients 32 .…”

Cancer Immunotherapy and Cytotoxicity: Current Advances and Challenges

“…Besides chimeric antigen receptor (CAR) transduction, T lymphocytes can also be genetically engineered with αβ T cell receptor expression, which is capable of recognizing MHC-restricted peptide antigens and therefore poised to turn into an important pillar of cellular cancer immunotherapy [82,111]. Generally, TCRs are capable of recognizing a relatively broad range of human leucocyte antigen (HLA)/ specific peptide that can be expressed in the surface of patient's T cells [112][113][114]. Therefore, TCR-Ts hold the potential to redirect the recognition of tumor-associated surface antigens and the removal of cancer cells.…”