Journal ArticleDOI
Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire
Ryan O. Emerson,William S DeWitt,Marissa Vignali,Jenna Gravley,Joyce K. Hu,Edward J. Osborne,Cindy Desmarais,Mark Klinger,Christopher S. Carlson,John A. Hansen,Mark J. Rieder,Harlan Robins +11 more
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TLDR
A statistical classification framework is developed that could diagnose CMV status from the resulting catalog of TCRβ sequences with high specificity and sensitivity in both the original cohort and a validation cohort of 120 different subjects.Abstract:
Ryan Emerson and colleagues report immunosequencing of the variable region of the TCRβ chain in 666 individuals with known cytomegalovirus (CMV) status. They show that CMV status and HLA genotype shape the T cell repertoire and demonstrate proof of principle that TCRβ sequencing can be used as a specific diagnostic of pathogen exposure. An individual's T cell repertoire dynamically encodes their pathogen exposure history. To determine whether pathogen exposure signatures can be identified by documenting public T cell receptors (TCRs), we profiled the T cell repertoire of 666 subjects with known cytomegalovirus (CMV) serostatus by immunosequencing. We developed a statistical classification framework that could diagnose CMV status from the resulting catalog of TCRβ sequences with high specificity and sensitivity in both the original cohort and a validation cohort of 120 different subjects. We also confirmed that three of the identified CMV-associated TCRβ molecules bind CMV in vitro, and, moreover, we used this approach to accurately predict the HLA-A and HLA-B alleles of most subjects in the first cohort. As all memory T cell responses are encoded in the common format of somatic TCR recombination, our approach could potentially be generalized to a wide variety of disease states, as well as other immunological phenotypes, as a highly parallelizable diagnostic strategy.read more
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The landscape of antigen-specific T cells in human cancers
Bo Li,Longchao Liu,Jian Zhang,Jiahui Chen,Jianfeng Ye,Alexander Filatenkov,Sachet A. Shukla,Jian Qiao,Xiaowei Zhan,Catherine J. Wu,Yang Xin Fu +10 more
TL;DR: This work leveraged previous efforts on tumor TCR repertoire, and developed a novel algorithm to characterize antigen-specific TCR clusters, and identified cancer-associated T cells with broad utilities in immune monitoring and cancer immunotherapies.
Journal ArticleDOI
Preexisting memory CD4 T cells in naïve individuals confer robust immunity upon hepatitis B vaccination
George Elias,Pieter Meysman,Esther Bartholomeus,Nicolas De Neuter,Nina Keersmaekers,Arvid Suls,Hilde Jansens,Aisha Souquette,Hans De Reu,Marie-Paule Emonds,Evelien Smits,Eva Lion,Paul G. Thomas,Geert Mortier,Pierre Van Damme,Philippe Beutels,Kris Laukens,Viggo Van Tendeloo,Benson Ogunjimi +18 more
TL;DR: High-throughput sequencing of memory CD4 TCRβ repertoire and machine learning are used to show that individuals with preexisting vaccine-reactive memory T cell clonotypes elicited earlier and higher antibody titers and mounted a more robustCD4 T cell response to hepatitis B vaccine.
Journal ArticleDOI
TCRpower: quantifying the detection power of T-cell receptor sequencing with a novel computational pipeline calibrated by spike-in sequences
Shiva Dahal-Koirala,Gabriel Balaban,Ralf Stefan Neumann,Lonneke Scheffer,Knut E.A. Lundin,Victor Greiff,Ludvig M. Sollid,Shuo-Wang Qiao,Geir Kjetil Sandve +8 more
TL;DR: TCRpower is publicly available and can be used to optimize future TCR sequencing experiments, and thereby enable reliable detection of disease-relevant TCRs for diagnostic applications.
Journal ArticleDOI
Heterologous Immunity of Virus-Specific T Cells Leading to Alloreactivity: Possible Implications for Solid Organ Transplantation
TL;DR: In this article, the authors provide an overview of murine and human studies investigating the incidence and functional properties of virus-specific memory T cells crossreacting with allo-antigens and discuss their potential relevance in the context of solid organ transplantation.
Journal ArticleDOI
Evolution and modulation of antigen-specific T cell responses in melanoma patients
Jani Huuhtanen,Liang Chen,Emmi Jokinen,Henna Kasanen,Tapio Lönnberg,Anna Kreutzman,Katriina Peltola,Micaela Hernberg,Chunlin Wang,Cassian Yee,Harri Lähdesmäki,Mark M. Davis,Satu Mustjoki +12 more
TL;DR: In this article , the authors analyzed three types of T cell receptor (TCR) repertoire data (antigen-specific TCRs, TCR-repertoire, and single-cell RNA + TCRαβ-sequencing data) from 515 patients with primary or metastatic melanoma and compare it to 783 healthy controls.
References
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Journal ArticleDOI
Statistical significance for genomewide studies
John D. Storey,Robert Tibshirani +1 more
TL;DR: This work proposes an approach to measuring statistical significance in genomewide studies based on the concept of the false discovery rate, which offers a sensible balance between the number of true and false positives that is automatically calibrated and easily interpreted.
Journal ArticleDOI
T-cell antigen receptor genes and T-cell recognition.
Mark M. Davis,Pamela J. Bjorkman +1 more
TL;DR: This view of T-cell recognition has implications for how the receptors might be selected in the thymus and how they (and immunoglobulins) may have arisen during evolution.
Journal ArticleDOI
Comprehensive assessment of T-cell receptor β-chain diversity in αβ T cells
Harlan Robins,Paulo Vidal Campregher,Santosh Srivastava,Abigail Wacher,Cameron J. Turtle,Cameron J. Turtle,Orsalem J. Kahsai,Stanley R. Riddell,Stanley R. Riddell,Edus H. Warren,Edus H. Warren,Christopher S. Carlson +11 more
TL;DR: A novel experimental and computational approach is developed to measure TCR CDR3 diversity based on single-molecule DNA sequencing, and it is found that total TCRbeta receptor diversity is at least 4-fold higher than previous estimates, and the diversity in the subset of CD45RO(+) antigen-experienced alphabeta T cells is at at least 10-foldHigher than previously estimates.
Journal ArticleDOI
Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see).
TL;DR: It is discussed how the particular composition of the peptide–MHC ligandomes that are presented by specific APC subsets not only shapes the T cell repertoire in the thymus but may also indelibly imprint the behaviour of mature T cells in the periphery.
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