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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Journal ArticleDOI
IgM Antibody Repertoire Fingerprints in Mice Are Personalized but Robust to Viral Infection Status.
Alexander Yermanos,Nike Julia Krautler,Alessandro Pedrioli,Ulrike Menzel,Victor Greiff,Tanja Stadler,Annette Oxenius,Sai T. Reddy +7 more
TL;DR: Compared the IgM repertoires from both blood and bone marrow plasma cells following acute or chronic lymphocytic choriomeningitis virus (LCMV) infection in mice revealed mouse-specific repertoire fingerprints between the blood and PC repertoires irrespective of infection status.
Journal ArticleDOI
A Conserved TCRβ Signature Dominates a Highly Polyclonal T-Cell Expansion During the Acute Phase of a Murine Malaria Infection.
Natasha L. Smith,Wiebke Nahrendorf,Catherine Sutherland,Jason P. Mooney,Joanne Thompson,Philip J Spence,Graeme J. M. Cowan +6 more
TL;DR: It is shown that following a first infection - within a highly polyclonal expansion - T-effector repertoires are consistently dominated by TRBV3 gene usage, and clustering by sequence similarity, it is found the same dominant clonal signature is expanded across replicates in the acute phase of an infection.
Journal ArticleDOI
T cell Repertoire Profiling and the Mechanism by which HLA-B27 Causes Ankylosing Spondylitis
TL;DR: In this paper , the authors describe findings of studies in ankylosing spondylitis involving profiling of T cell expansions and discuss future research opportunities based on these findings, which strongly support the theory that AS is driven by presentation of antigenic peptides to the adaptive immune system by HLA-B27.
Journal ArticleDOI
Reference-based comparison of adaptive immune receptor repertoires
Cédric R. Weber,Teresa Rubio,Longlong Wang,Wei Zhang,Philippe Robert,Rahmad Akbar,Igor Snapkov,Jinghua Wu,Marieke L. Kuijjer,Sonia Tarazona,Ana Conesa,Geir Kjetil Sandve,Xiao Sheng Liu,Sai T. Reddy,Victor Greiff +14 more
TL;DR: The authors The authors is a quantitative multidimensional measure of adaptive immune repertoire and transcriptome similarity that allows interpretation of immune repertoire variation by relying on both repertoire features and cross-referencing of simulated and experimental datasets.
Journal ArticleDOI
Antigen receptor repertoires of one of the smallest known vertebrates
Orlando Bruno Giorgetti,Prashant Shingate,Connor P. O'Meara,Vydianathan Ravi,Nisha E. Pillai,Boon-Hui Tay,Aravind Prasad,Norimasa Iwanami,Heok Hui Tan,Michael Schorpp,Byrappa Venkatesh,Thomas Boehm +11 more
TL;DR: In this article, the authors studied the immunogenetic features of one of the smallest known vertebrates, the cyprinid fish Paedocypris sp. "Singkep" ("minifish").
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.
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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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