scholarly journals Ultra-Efficient Short Read Sequencing of T Cell Receptor Repertoires

2018 ◽  
Author(s):  
Janelle M. Montagne ◽  
Xuwen Alice Zheng ◽  
Iago Pinal-Fernandez ◽  
Jose C. Milisenda ◽  
Lisa Christopher-Stine ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Large Scale ◽  
Cell Receptor ◽  
Short Read ◽  
Industry Standards ◽  
Tcr Repertoire ◽  
Sporadic Inclusion Body Myositis ◽  
Repertoire Sequencing ◽  
Primer Sets

Abstract:T cell receptor (TCR) repertoire sequencing is increasingly employed to characterize adaptive immune responses. However, current TCR sequencing methodologies are complex and expensive, limiting the scale of feasible studies. Here we present Framework Region 3 AmplifiKation sequencing (FR3AK-seq), a simplified multiplex PCR-based approach for the ultra-efficient analysis of TCR complementarity determining region 3 (CDR3) repertoires. By using minimal primer sets targeting a conserved region adjacent to CDR3, undistorted amplicons are analyzed via short read, single-end sequencing. We find that FR3AK-seq is sensitive and quantitative, performing comparably to two industry standards. FR3AK-seq was utilized to quickly and inexpensively characterize the T cell infiltrates of muscle biopsies obtained from 145 patients with idiopathic inflammatory myopathies and controls. A cluster of related TCRs was identified in samples from patients with sporadic inclusion body myositis, suggesting the presence of a shared antigen-driven response. The ease and minimal cost of FR3AK-seq removes critical barriers to routine, large-scale TCR CDR3 repertoire analyses.

scholarly journals PDCT-12. TRACKING T-CELL IMMUNE RECONSTITUTION AFTER ADOPTIVE CELLULAR THERAPY TARGETING RECURRENT MEDULLOBLASTOMA AND PNETS USING DEEP T-CELL RECEPTOR (TCR) REPERTOIRE SEQUENCING

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi186-vi186
Author(s):  
Oleg Yegorov ◽  
Yanina Yegorova ◽  
Anjelika Dechkovskaia ◽  
Jianping Huang ◽  
Sridharan Gururangan ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Immune Reconstitution ◽  
Cellular Therapy ◽  
Cell Receptor ◽  
Adoptive Cellular Therapy ◽  
Tcr Repertoire ◽  
Repertoire Sequencing

scholarly journals VDJdb in 2019: database extension, new analysis infrastructure and a T-cell receptor motif compendium

2019 ◽  
Vol 48 (D1) ◽  
pp. D1057-D1062 ◽  
Author(s):  
Dmitry V Bagaev ◽  
Renske M A Vroomans ◽  
Jerome Samir ◽  
Ulrik Stervbo ◽  
Cristina Rius ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Large Datasets ◽  
Real World Data ◽  
Identification Methods ◽  
Database Querying ◽  
Tcr Repertoire ◽  
Repertoire Sequencing ◽  
On Line

Abstract Here, we report an update of the VDJdb database with a substantial increase in the number of T-cell receptor (TCR) sequences and their cognate antigens. The update further provides a new database infrastructure featuring two additional analysis modes that facilitate database querying and real-world data analysis. The increased yield of TCR specificity identification methods and the overall increase in the number of studies in the field has allowed us to expand the database more than 5-fold. Furthermore, several new analysis methods are included. For example, batch annotation of TCR repertoire sequencing samples allows for annotating large datasets on-line. Using recently developed bioinformatic methods for TCR motif mining, we have built a reduced set of high-quality TCR motifs that can be used for both training TCR specificity predictors and matching against TCRs of interest. These additions enhance the versatility of the VDJdb in the task of exploring T-cell antigen specificities. The database is available at https://vdjdb.cdr3.net.

Serial T-cell Receptor (TCR) Repertoire Sequencing to Predict Outcomes in Gastrointestinal (GI) Malignancies

2020 ◽  
Vol 108 (3) ◽  
pp. S110
Author(s):  
D.W. Kim ◽  
J.M. Heather ◽  
G. Lee ◽  
S.M. Sepulveda ◽  
E. Van Seventer ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Tcr Repertoire ◽  
Repertoire Sequencing

scholarly journals GIANA allows computationally-efficient TCR clustering and multi-disease repertoire classification by isometric transformation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hongyi Zhang ◽  
Xiaowei Zhan ◽  
Bo Li
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Large Scale ◽  
Cell Receptor ◽  
Alignment Algorithm ◽  
Computationally Efficient ◽  
Antigen Specificity ◽  
Non Invasive ◽  
Isometric Transformation ◽  
Specific Receptors

AbstractSimilarity in T-cell receptor (TCR) sequences implies shared antigen specificity between receptors, and could be used to discover novel therapeutic targets. However, existing methods that cluster T-cell receptor sequences by similarity are computationally inefficient, making them impractical to use on the ever-expanding datasets of the immune repertoire. Here, we developed GIANA (Geometric Isometry-based TCR AligNment Algorithm) a computationally efficient tool for this task that provides the same level of clustering specificity as TCRdist at 600 times its speed, and without sacrificing accuracy. GIANA also allows the rapid query of large reference cohorts within minutes. Using GIANA to cluster large-scale TCR datasets provides candidate disease-specific receptors, and provides a new solution to repertoire classification. Querying unseen TCR-seq samples against an existing reference differentiates samples from patients across various cohorts associated with cancer, infectious and autoimmune disease. Our results demonstrate how GIANA could be used as the basis for a TCR-based non-invasive multi-disease diagnostic platform.

scholarly journals The Distribution of Gene Segments in T-Cell Receptor γ Gene Rearrangements Demonstrates the Need for Multiple Primer Sets

2003 ◽  
Vol 5 (2) ◽  
pp. 82-87 ◽  
Author(s):  
Lyle C. Lawnicki ◽  
Ronald J. Rubocki ◽  
Wing C. Chan ◽  
Deborah M. Lytle ◽  
Timothy C. Greiner
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Gene Rearrangements ◽  
Primer Sets

scholarly journals Large-scale proteomic analysis of tyrosine-phosphorylation induced by T-cell receptor or B-cell receptor activation reveals new signaling pathways

PROTEOMICS ◽  
2009 ◽  
Vol 9 (13) ◽  
pp. 3549-3563 ◽  
Author(s):  
Masaki Matsumoto ◽  
Koji Oyamada ◽  
Hidehisa Takahashi ◽  
Takamichi Sato ◽  
Shigetsugu Hatakeyama ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Signaling Pathways ◽  
Tyrosine Phosphorylation ◽  
T Cell Receptor ◽  
Proteomic Analysis ◽  
Large Scale ◽  
Cell Receptor ◽  
Receptor Activation ◽  
B Cell Receptor

scholarly journals Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
William S DeWitt ◽  
Anajane Smith ◽  
Gary Schoch ◽  
John A Hansen ◽  
Frederick A Matsen ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Genetic Background ◽  
Cell Receptor ◽  
Sequencing Data ◽  
Human T Cell ◽  
Disease Associations ◽  
Repertoire Sequencing ◽  
Mhc Polymorphism ◽  
Occurrence Patterns

The T cell receptor (TCR) repertoire encodes immune exposure history through the dynamic formation of immunological memory. Statistical analysis of repertoire sequencing data has the potential to decode disease associations from large cohorts with measured phenotypes. However, the repertoire perturbation induced by a given immunological challenge is conditioned on genetic background via major histocompatibility complex (MHC) polymorphism. We explore associations between MHC alleles, immune exposures, and shared TCRs in a large human cohort. Using a previously published repertoire sequencing dataset augmented with high-resolution MHC genotyping, our analysis reveals rich structure: striking imprints of common pathogens, clusters of co-occurring TCRs that may represent markers of shared immune exposures, and substantial variations in TCR-MHC association strength across MHC loci. Guided by atomic contacts in solved TCR:peptide-MHC structures, we identify sequence covariation between TCR and MHC. These insights and our analysis framework lay the groundwork for further explorations into TCR diversity.

scholarly journals A Framework to Identify Antigen-Expanded T Cell Receptor Clusters Within Complex Repertoires

2021 ◽  
Vol 12 ◽  
Author(s):  
Valentina Ceglia ◽  
Erin J. Kelley ◽  
Annalee S. Boyle ◽  
Sandra Zurawski ◽  
Heather L. Mead ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Antigen Specificity ◽  
Protein Antigens ◽  
Cell Responses ◽  
Tcr Repertoire ◽  
Receptor Clusters ◽  
Theoretical Sensitivity

Common approaches for monitoring T cell responses are limited in their multiplexity and sensitivity. In contrast, deep sequencing of the T Cell Receptor (TCR) repertoire provides a global view that is limited only in terms of theoretical sensitivity due to the depth of available sampling; however, the assignment of antigen specificities within TCR repertoires has become a bottleneck. This study combines antigen-driven expansion, deep TCR sequencing, and a novel analysis framework to show that homologous ‘Clusters of Expanded TCRs (CETs)’ can be confidently identified without cell isolation, and assigned to antigen against a background of non-specific clones. We show that clonotypes within each CET respond to the same epitope, and that protein antigens stimulate multiple CETs reactive to constituent peptides. Finally, we demonstrate the personalized assignment of antigen-specificity to rare clones within fully-diverse uncultured repertoires. The method presented here may be used to monitor T cell responses to vaccination and immunotherapy with high fidelity.

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