Publisher Correction: Human γδ T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection

Ravens, Sarina; Schultze-Florey, Christian; Raha, Solaiman; Sandrock, Inga; Drenker, Melanie; Oberdörfer, Linda; Reinhardt, Annika; Ravens, Inga; Beck, Maleen; Geffers, Robert; Kaisenberg, Constantin von; Heuser, Michael; Thol, Felicitas; Ganser, Arnold; Förster, Reinhold; Koenecke, Christian; Prinz, Immo

doi:10.1038/s41590-018-0054-x

Cited by 3 publications

(3 citation statements)

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“…tcrsampler is a tool for subsampling large bulk datasets to estimate the frequency of TCRs and TCR neighborhoods in background repertoires. The module comes with large, bulk sequenced, default databases for human TCR α, β, γ, and δ and mouse TCR β ( Britanova et al, 2016 ; Ravens et al, 2018 ; Wirasinha et al, 2018 ). Datasets were selected because they represented the largest preantigen exposure TCR repertoires available; users can optionally supply their own background repertoires when applicable.…”

Section: Methodsmentioning

confidence: 99%

TCR meta-clonotypes for biomarker discovery with tcrdist3 enabled identification of public, HLA-restricted clusters of SARS-CoV-2 TCRs

Mayer-Blackwell

Schattgen

Cohen-Lavi

et al. 2021

eLife

111

109

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T-cell receptors (TCRs) encode clinically valuable information that reflects prior antigen exposure and potential future response. However, despite advances in deep repertoire sequencing, enormous TCR diversity complicates the use of TCR clonotypes as clinical biomarkers. We propose a new framework that leverages experimentally inferred antigen-associated TCRs to form meta-clonotypes – groups of biochemically similar TCRs – that can be used to robustly quantify functionally similar TCRs in bulk repertoires across individuals. We apply the framework to TCR data from COVID-19 patients, generating 1831 public TCR meta-clonotypes from the SARS-CoV-2 antigen-associated TCRs that have strong evidence of restriction to patients with a specific human leukocyte antigen (HLA) genotype. Applied to independent cohorts, meta-clonotypes targeting these specific epitopes were more frequently detected in bulk repertoires compared to exact amino acid matches, and 59.7% (1093/1831) were more abundant among COVID-19 patients that expressed the putative restricting HLA allele (false discovery rate [FDR]<0.01), demonstrating the potential utility of meta-clonotypes as antigen-specific features for biomarker development. To enable further applications, we developed an open-source software package, tcrdist3, that implements this framework and facilitates flexible workflows for distance-based TCR repertoire analysis.

show abstract

Section: Methodsmentioning

confidence: 99%

TCR meta-clonotypes for biomarker discovery with tcrdist3 enabled identification of public, HLA-restricted clusters of SARS-CoV-2 TCRs

Mayer-Blackwell

Schattgen

Cohen-Lavi

et al. 2021

eLife

111

109

View full text Add to dashboard Cite

show abstract

“…tcrsampler is a tool for sub-sampling large bulk datasets to estimate the frequency of TCRs and TCR neighborhoods in non-antigen-enriched background repertoires. The module comes with large, bulk sequenced, default databases for human TCR α, β, γ and δ and mouse TCR β (Britanova et al, 2016; Ravens et al, 2018; Wirasinha et al, 2018). Datasets were selected because they represented the largest pre-antigen exposure TCR repertoires available; users can optionally supply their own background repertoires when applicable.…”

Section: Methodsmentioning

confidence: 99%

TCR meta-clonotypes for biomarker discovery with tcrdist3: identification of public, HLA-restricted SARS-CoV-2 associated TCR features

Mayer-Blackwell

Schattgen

Cohen-Lavi

et al. 2020

Preprint

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As the mechanistic basis of adaptive cellular antigen recognition, T cell receptors (TCRs) encode clinically valuable information that reflects prior antigen exposure and potential future response. However, despite advances in deep repertoire sequencing, enormous TCR diversity complicates the use of TCR clonotypes as clinical biomarkers. We propose a new framework that leverages antigen-enriched repertoires to form meta-clonotypes – groups of biochemically similar TCRs – that can be used to robustly quantify functionally similar TCRs in bulk repertoires. We apply the framework to TCR data from COVID-19 patients, generating 1,915 public TCR meta-clonotypes from the 18 SARS-CoV-2 antigen-enriched repertoires with the strongest evidence of HLA-restriction. Applied to independent cohorts, meta-clonotypes targeting these specific epitopes were more frequently detected in bulk repertoires compared to exact amino acid matches, and 44% (845/1915) were significantly enriched among COVID-19 patients that expressed the putative restricting HLA allele, demonstrating the potential utility of meta-clonotypes as antigen-specific features for biomarker development. To enable further applications, we developed an open-source software package, tcrdist3, that implements this framework and facilitates workflows for distance-based TCR repertoire analysis.

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“…The γ/δ T cell repertoire seems to be established quite early after 30-60 days after allo-SCT. CMV reactivation promotes the massive expansion of a few γ/δ T cell subtypes (belonging mainly to the delta-1 subset) resulting in a so-called repertoire focusing [116]. Henceforth, DLI administration for prophylactic, preemptive and overt relapse, as well as treatment of prophylaxis of infections, or immune reconstitution might not only depend on the type of the disease, or the timing but also on the size of the α/β and γ/δ T cell repertoire monitored at a given time point.…”

Section: Five-year Viewmentioning

confidence: 99%

Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients

Greiner

Götz

Bunjes

et al. 2019

JCM

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Allogeneic stem cell transplantation (allo-SCT) is the preferred curative treatment for several hematological malignancies. The efficacy of allo-SCT depends on the graft-versus-leukemia (GvL) effect. However, the prognosis of patients with relapsed acute myeloid leukemia (AML) following allo-SCT is poor. Donor lymphocyte infusion (DLI) is utilized after allo-SCT in this setting to prevent relapse, to prolong progression free survival, to establish full donor chimerism and to restore the GvL effect in patients with hematological malignancies. Thus, there are different options for the administration of DLI in AML patients. DLI is currently used prophylactically and in the setting of an overt relapse. In addition, in the minimal residual disease (MRD) setting, DLI may be a possibility to improve overall survival. However, DLI might increase the risk of severe life-threatening complications such as graft-versus-host disease (GvHD) as well as severe infections. The transfusion of lymphocytes has been tested not only for the treatment of hematological malignancies but also chronic infections. In this context, manipulated DLI in a prophylactic or therapeutic approach are an option, e.g., virus-specific DLI using different selection methods or antigen-specific DLI such as peptide-specific CD8+ cytotoxic T lymphocytes (CTLs). In addition, T cells are also genetically engineered, using both chimeric antigen receptor (CAR) genetically modified T cells and T cell receptor (TCR) genetically modified T cells. T cell therapies in general have the potential to enhance antitumor immunity, augment vaccine efficacy, and limit graft-versus-host disease after allo-SCT. The focus of this review is to discuss the different strategies to use donor lymphocytes after allo-SCT. Our objective is to give an insight into the functional effects of DLI on immunogenic antigen recognition for a better understanding of the mechanisms of DLI. To ultimately increase the GvL potency without raising the risk of GvHD at the same time.

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Publisher Correction: Human γδ T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection

Cited by 3 publications

References 0 publications

TCR meta-clonotypes for biomarker discovery with tcrdist3 enabled identification of public, HLA-restricted clusters of SARS-CoV-2 TCRs

TCR meta-clonotypes for biomarker discovery with tcrdist3 enabled identification of public, HLA-restricted clusters of SARS-CoV-2 TCRs

TCR meta-clonotypes for biomarker discovery with tcrdist3: identification of public, HLA-restricted SARS-CoV-2 associated TCR features

Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients

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