In vitro-induced response patterns of antileukemic T cells: characterization by spectratyping and immunophenotyping

Reuther, Susanne; Schmetzer, Helga; Schuster, Friedhelm R.; Krell, Pina Fanny Ida; Grabrucker, Christine; Liepert, Anja; Kroell, Tanja; Kolb, Hans‐Jochem; Buhmann, Raymund

doi:10.1007/s10238-012-0180-y

Cited by 12 publications

(11 citation statements)

References 40 publications

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“…Schmetzer et al have shown that T-cell clonality was more restricted after ex vivo DC leu induction compared to blast stimulation, pointing to a role of DC leu to efficiently enrich selected T-cell-clones. Interestingly, T cells with the same Vβ chain of the T cell receptor that was observed in vivo were also found in in vitro cultures (131). …”

Section: Improvement Of the Responsementioning

confidence: 92%

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

et al. 2017

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The success of hematopoietic stem cell transplantation (HSCT) lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL), caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter.

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Section: Improvement Of the Responsementioning

confidence: 92%

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

et al. 2017

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“…This prediction has been verified for T cells in a wide variety of models, using antigen-specific readouts such as cytokine responses, and major histocompatibility complex (MHC) multimer binding to identify expanded lymphocyte clones (2–4). The selective expansion of specific clones has also been inferred from global measurements such as V region usage (5) or spectratyping (a technique sometimes referred to as the immunoscope) (6). The sequences of TCRs with a known antigen specificity have been examined previously, especially in the context of CD8+ T cells and influenza.…”

Section: Introductionmentioning

confidence: 99%

Specificity, Privacy, and Degeneracy in the CD4 T Cell Receptor Repertoire Following Immunization

Sun¹,

Best²,

Cinelli³

et al. 2017

Front. Immunol.

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T cells recognize antigen using a large and diverse set of antigen-specific receptors created by a complex process of imprecise somatic cell gene rearrangements. In response to antigen-/receptor-binding-specific T cells then divide to form memory and effector populations. We apply high-throughput sequencing to investigate the global changes in T cell receptor sequences following immunization with ovalbumin (OVA) and adjuvant, to understand how adaptive immunity achieves specificity. Each immunized mouse contained a predominantly private but related set of expanded CDR3β sequences. We used machine learning to identify common patterns which distinguished repertoires from mice immunized with adjuvant with and without OVA. The CDR3β sequences were deconstructed into sets of overlapping contiguous amino acid triplets. The frequencies of these motifs were used to train the linear programming boosting (LPBoost) algorithm LPBoost to classify between TCR repertoires. LPBoost could distinguish between the two classes of repertoire with accuracies above 80%, using a small subset of triplet sequences present at defined positions along the CDR3. The results suggest a model in which such motifs confer degenerate antigen specificity in the context of a highly diverse and largely private set of T cell receptors.

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“…This prediction has been verified for T cells in a wide variety of models, using antigen-specific readouts such as cytokine responses, and Major Histocompatibility Complex (MHC) multimer binding to identify expanded lymphocyte clones (Catron et al , 2004; Hataye et al , 2006; Moon et al , 2007). The selective expansion of specific clones has also been inferred from global measurements such as V region usage (Reuther et al , 2013) or spectratyping (a technique sometimes referred to as the immunoscope) (Russi et al , 2013). Previous studies have distinguished between private T-cell receptors (TcRs), found in one or a few individuals, and public TcRs found within the responding repertoire of a majority of individuals.…”

Section: Introductionmentioning

confidence: 99%

Tracking global changes induced in the CD4 T-cell receptor repertoire by immunization with a complex antigen using short stretches of CDR3 protein sequence

et al. 2014

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Motivation: The clonal theory of adaptive immunity proposes that immunological responses are encoded by increases in the frequency of lymphocytes carrying antigen-specific receptors. In this study, we measure the frequency of different T-cell receptors (TcR) in CD4 + T cell populations of mice immunized with a complex antigen, killed Mycobacterium tuberculosis, using high throughput parallel sequencing of the TcRβ chain. Our initial hypothesis that immunization would induce repertoire convergence proved to be incorrect, and therefore an alternative approach was developed that allows accurate stratification of TcR repertoires and provides novel insights into the nature of CD4 + T-cell receptor recognition.Results: To track the changes induced by immunization within this heterogeneous repertoire, the sequence data were classified by counting the frequency of different clusters of short (3 or 4) continuous stretches of amino acids within the antigen binding complementarity determining region 3 (CDR3) repertoire of different mice. Both unsupervised (hierarchical clustering) and supervised (support vector machine) analyses of these different distributions of sequence clusters differentiated between immunized and unimmunized mice with 100% efficiency. The CD4 + TcR repertoires of mice 5 and 14 days postimmunization were clearly different from that of unimmunized mice but were not distinguishable from each other. However, the repertoires of mice 60 days postimmunization were distinct both from naive mice and the day 5/14 animals. Our results reinforce the remarkable diversity of the TcR repertoire, resulting in many diverse private TcRs contributing to the T-cell response even in genetically identical mice responding to the same antigen. However, specific motifs defined by short stretches of amino acids within the CDR3 region may determine TcR specificity and define a new approach to TcR sequence classification.Availability and implementation: The analysis was implemented in R and Python, and source code can be found in Supplementary Data.Contact: b.chain@ucl.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.

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In vitro-induced response patterns of antileukemic T cells: characterization by spectratyping and immunophenotyping

Cited by 12 publications

References 40 publications

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

Specificity, Privacy, and Degeneracy in the CD4 T Cell Receptor Repertoire Following Immunization

Tracking global changes induced in the CD4 T-cell receptor repertoire by immunization with a complex antigen using short stretches of CDR3 protein sequence

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