scholarly journals Modeling and predicting the overlap of B- and T-cell receptor repertoires in healthy and SARS-CoV-2 infected individuals

2021 ◽  
Author(s):  
Maria Ruiz Ortega ◽  
Natanael Spisak ◽  
Thierry Mora ◽  
Aleksandra M Walczak
Keyword(s):  
T Cell ◽  
Statistical Approach ◽  
Cell Receptor ◽  
High Accuracy ◽  
Accurate Diagnosis ◽  
Healthy Individuals ◽  
Protein Receptors ◽  
Repertoire Diversity ◽  
Diagnosis Tool ◽  
Selection Factor

Adaptive immunity's success relies on the extraordinary diversity of protein receptors on B and T cell membranes. Despite this diversity, the existence of public receptors shared by many individuals gives hope for developing population wide vaccines and therapeutics. Yet many of these public receptors are shared by chance. We present a statistical approach, defined in terms of a probabilistic V(D)J recombination model enhanced by a selection factor, that describes repertoire diversity and predicts with high accuracy the spectrum of repertoire overlap in healthy individuals. The model underestimates sharing between repertoires of individuals infected with SARS-CoV-2, suggesting strong antigen-driven convergent selection. We exploit this discrepancy to identify COVID-associated receptors, which we validate against datasets of receptors with known viral specificity. We study their properties in terms of sequence features and network organization, and use them to design an accurate diagnosis tool for predicting SARS-CoV-2 status from repertoire data.

scholarly journals Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups

iScience ◽  
2021 ◽  
Vol 24 (2) ◽  
pp. 102053
Author(s):  
Sanghoon Lee ◽  
Li Zhao ◽  
Latasha D. Little ◽  
Shannon N. Westin ◽  
Amir A. Jazarei ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Receptor Repertoire ◽  
Repertoire Diversity ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

scholarly journals Altered Repertoire Diversity and Disease‐Associated Clonal Expansions Revealed by T Cell Receptor Immunosequencing in Ankylosing Spondylitis Patients

2020 ◽  
Vol 72 (8) ◽  
pp. 1289-1302 ◽  
Author(s):  
Aimee L. Hanson ◽  
Hendrik J. Nel ◽  
Linda Bradbury ◽  
Julie Phipps ◽  
Ranjeny Thomas ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Repertoire Diversity

scholarly journals Systematic profiling of full-length immunoglobulin and T-cell receptor repertoire diversity in rhesus macaque through long read transcriptome sequencing

2019 ◽  
Author(s):  
Hayden N. Brochu ◽  
Elizabeth Tseng ◽  
Elise Smith ◽  
Matthew J. Thomas ◽  
Aiden Jones ◽  
...  
Keyword(s):  
T Cell ◽  
Rhesus Macaque ◽  
T Cell Receptor ◽  
Focal Point ◽  
Cell Receptor ◽  
Full Length ◽  
Variable Regions ◽  
Tcr Repertoire ◽  
Long Read ◽  
Repertoire Diversity

AbstractThe diversity of immunoglobulin (Ig) and T-cell receptor (TCR) repertoires is a focal point of immunological studies. Rhesus macaques are key for modeling human immune responses, placing critical importance on the accurate annotation and quantification of their Ig and TCR repertoires. However, due to incomplete reference resources, the coverage and accuracy of the traditional targeted amplification strategies for profiling rhesus Ig and TCR repertoires are largely unknown. Here, using long read sequencing, we sequenced four Indian-origin rhesus macaque tissues and obtained high quality, full-length sequences for over 6,000 unique Ig and TCR transcripts, without the need for sequence assembly. We constructed the first complete reference set for the constant regions of all known isotypes and chain types of rhesus Ig and TCR repertoires. We show that sequence diversity exists across the entire variable regions of rhesus Ig and TCR transcripts. Consequently, existing strategies using targeted amplification of rearranged variable regions comprised of V(D)J gene segments miss a significant fraction (27% to 53% and 42% to 49%) of rhesus Ig/TCR diversity. To overcome these limitations, we designed new rhesus-specific assays that remove the need for primers conventionally targeting variable regions and allow single cell-level Ig and TCR repertoire analysis. Our improved approach will enable future studies to fully capture rhesus Ig and TCR repertoire diversity and is applicable for improving annotations in any model organism.

scholarly journals T Cell Receptor Repertoire Diversity and Clonal Expansion in Human Neonates

1998 ◽  
Vol 43 (3) ◽  
pp. 396-402 ◽  
Author(s):  
Robert L Schelonka ◽  
Frank M Raaphorst ◽  
Diane Infante ◽  
Ellen Kraig ◽  
Judy M Teale ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
Receptor Repertoire ◽  
Repertoire Diversity ◽  
T Cell Receptor Repertoire ◽  
Human Neonates ◽  
Cell Receptor Repertoire

scholarly journals Characterization of the TCR β Chain CDR3 Repertoire in Subarachnoid Hemorrhage Patients with Delayed Cerebral Ischemia

2020 ◽  
Vol 21 (9) ◽  
pp. 3149 ◽  
Author(s):  
Bong Jun Kim ◽  
Dong Hyuk Youn ◽  
Youngmi Kim ◽  
Jin Pyeong Jeon
Keyword(s):  
Subarachnoid Hemorrhage ◽  
T Cell ◽  
Cerebral Ischemia ◽  
High Throughput Sequencing ◽  
Delayed Cerebral Ischemia ◽  
Adaptive Immune Response ◽  
Cell Receptor ◽  
P Value ◽  
Repertoire Diversity ◽  
Β Chain

Little is known of the adaptive immune response to subarachnoid hemorrhage (SAH). This study was the first to investigate whether T cell receptor (TCR) immune repertoire may provide a better understanding of T cell immunology in delayed cerebral ischemia (DCI). We serially collected peripheral blood in five SAH patients with DCI. High-throughput sequencing was used to analyze the TCR β chain (TCRB) complimentary determining regions (CDR) 3 repertoire. We evaluated the compositions and variations of the repertoire between admission and the DCI period, for severe DCI and non-severe DCI patients. Clonality did not differ significantly between admission and DCI. Severe DCI patients had significantly lower clonality than non-severe DCI patients (p value = 0.019). A read frequency of 0.005% ≤ – < 0.05% dominated the clonal expansion in non-severe DCI patients. Regarding repertoire diversity, severe DCI had a higher diversity score on admission than non-severe DCI. The CDR3 lengths were similar between admission and DCI. Among 728 annotated V-J gene pairs, we found that the relative frequencies of two V-J pairs were different at the occurrence of DCI than at admission, with T cells increasing by over 15%. TCRB CDR3 repertoires may serve as biomarkers to identify severe DCI patients.

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