Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes

Bentzen, Amalie Kai; Marquard, Andrea Marion; Lyngaa, Rikke; Saini, Sunil Kumar; Ramskov, Sofie; Donia, Marco; Such, Lina; Furness, Andrew; McGranahan, Nicholas; Rosenthal, Rachel; Straten, Per thor; Szállási, Zoltán; Svane, Inge Marie; Swanton, Charles; Quezada, Sergio A.; Jakobsen, Søren Nyboe; Eklund, Aron C.; Hadrup, Sine Reker

doi:10.1038/nbt.3662

Cited by 286 publications

(303 citation statements)

References 52 publications

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“…The development of new peptide-MHC multimeric complexes supports the detection and isolation of antigen-specific lymphocytes at much lower frequencies [108] than was previously feasible. New methods have been recently developed to provide high-throughput single cell repertoire sequencing of B and T lymphocytes [109•,110]. …”

Section: The Future Of Single Cell Immunoprofilingmentioning

confidence: 99%

Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis

Fonseka

Rao

Raychaudhuri

2017

Current Opinion in Immunology

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CD4+ T cells have been long known to play an important role in the pathogenesis of rheumatoid arthritis (RA), but the specific cell populations and states that drive the disease have been challenging to identify with low dimensional single cell data and bulk assays. The advent of high dimensional single cell technologies – like single cell RNA-seq or mass cytometry – has offered promise to defining key populations, but brings new methodological and statistical challenges. Recent single cell profiling studies have revealed a broad diversity of cell types among CD4+ T cells, identifying novel populations that are expanded or altered in RA. Here we will review recent findings on CD4+ T cell heterogeneity and RA that have come from single cell profiling studies and discuss the best practices for conducting these studies.

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Section: The Future Of Single Cell Immunoprofilingmentioning

confidence: 99%

Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis

Fonseka

Rao

Raychaudhuri

2017

Current Opinion in Immunology

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“…Mass cytometry has expanded the number of channels that can be utilized for a single cell but that number remains in the double digits. Interestingly, a recent study has described a method capable of costaining 1 peripheral blood sample with 1000 different pMHC multimers by conjugating each type of multimer to a unique DNA barcode 54 . The proportion of T cells with each pMHC specificity is then determined by sorting all multimer-bound cells (identified by conjugation of all pMHC multimers to 1 common fluorophore), sequencing the barcodes in the sorted population to enable functional T cell analysis with large-scale epitope recognition profiling for various diseases.…”

Section: Studying the Polyclonal Allospecific T Repertoire With Pmhc mentioning

confidence: 99%

Evolving Approaches in the Identification of Allograft-Reactive T and B Cells in Mice and Humans

Young

McIntosh²,

Alegre³

et al. 2017

Transplantation

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Whether a transplanted allograft is stably accepted, rejected or achieves immunological tolerance is dependent on the frequency and function of alloreactive lymphocytes, making the identification and analysis of alloreactive T and B cells in transplant recipients critical for understanding mechanisms, and the prediction of allograft outcome. In animal models, tracking the fate of graft-reactive T and B cells allows investigators to uncover their biology and develop new therapeutic strategies to protect the graft. In the clinic, identification and quantification of graft-reactive T and B cells allows for the early diagnosis of immune reactivity and therapeutic intervention to prevent graft loss. In addition to rejection, probing of T and B cell fate in vivo provides insights into the underlying mechanisms of alloimmunity or tolerance that may lead to biomarkers predicting graft fate. In this review, we discuss existing and developing approaches to track and analyze alloreactive T and B cells in mice and humans and provide examples of discoveries made utilizing these techniques. These approaches include mixed lymphocyte reactions (MLRs), trans-vivo delayed-type hypersensitivity (DTH), enzyme-linked immunospot (ELISpot) assays, the use of antigen receptor transgenic lymphocytes, and utilization of peptide-MHC complex (pMHC) multimers, along with imaging techniques for static multiparameter analysis or dynamic in vivo tracking. Such approaches have already refined our understanding of the alloimmune response and are pointing to new ways to improve allograft outcomes in the clinic.

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“…Accordingly, screening for a large peptide library will thus require a large amount of patient material. To address this problem, a novel technology with DNA barcode-labeled peptide-MHC multimers to increase the possibly covered complexity has recently been introduced [54]. This technology uses an oligonucleotide to form a barcode tag that is associated to the identity of a given peptide–MHC complex, allowing the mixing of > 1000 T-cell specificities.…”

Section: Introductionmentioning

confidence: 99%

Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC

Becker

Stang

Hausen

et al. 2017

Cancer Immunol Immunother

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Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations affect comparable signaling pathways such as RB restriction of cell cycle progression or p53 inactivation. Despite its low incidence, MCC recently received much attention based on its exquisite immunogenicity and the resulting major success of immune modulating therapies. Here, we summarize current knowledge on epidemiology, biology and therapy of MCC as conclusion of the project ‘Immune Modulating strategies for treatment of Merkel Cell Carcinoma’, which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC.

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Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes

Cited by 286 publications

References 52 publications

Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis

Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis

Evolving Approaches in the Identification of Allograft-Reactive T and B Cells in Mice and Humans

Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC

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