scholarly journals Immunosenescence and Autoimmunity: Exploiting the T-Cell Receptor Repertoire to Investigate the Impact of Aging on Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberta Amoriello ◽  
Alice Mariottini ◽  
Clara Ballerini
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
T Cell Receptor ◽  
High Throughput Sequencing ◽  
Cell Receptor ◽  
Receptor Repertoire ◽  
Age Related ◽  
Tcr Repertoire ◽  
Repertoire Diversity ◽  
The Impact

T-cell receptor (TCR) repertoire diversity is a determining factor for the immune system capability in fighting infections and preventing autoimmunity. During life, the TCR repertoire diversity progressively declines as a physiological aging progress. The investigation of TCR repertoire dynamics over life represents a powerful tool unraveling the impact of immunosenescence in health and disease. Multiple Sclerosis (MS) is a demyelinating, inflammatory, T-cell mediated autoimmune disease of the Central Nervous System in which age is crucial: it is the most widespread neurological disease among young adults and, furthermore, patients age may impact on MS progression and treatments outcome. Crossing knowledge on the TCR repertoire dynamics over MS patients’ life is fundamental to investigate disease mechanisms, and the advent of high- throughput sequencing (HTS) has significantly increased our knowledge on the topic. Here we report an overview of current literature about the impact of immunosenescence and age-related TCR dynamics variation in autoimmunity, including MS.

scholarly journals TCRMatch: Predicting T-Cell Receptor Specificity Based on Sequence Similarity to Previously Characterized Receptors

2021 ◽  
Vol 12 ◽  
Author(s):  
William D. Chronister ◽  
Austin Crinklaw ◽  
Swapnil Mahajan ◽  
Randi Vita ◽  
Zeynep Koşaloğlu-Yalçın ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
High Throughput Sequencing ◽  
Sequence Similarity ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
Epitope Specificity ◽  
Receptor Repertoire ◽  
Tcr Repertoire ◽  
Specific Receptors

The adaptive immune system in vertebrates has evolved to recognize non-self antigens, such as proteins expressed by infectious agents and mutated cancer cells. T cells play an important role in antigen recognition by expressing a diverse repertoire of antigen-specific receptors, which bind epitopes to mount targeted immune responses. Recent advances in high-throughput sequencing have enabled the routine generation of T-cell receptor (TCR) repertoire data. Identifying the specific epitopes targeted by different TCRs in these data would be valuable. To accomplish that, we took advantage of the ever-increasing number of TCRs with known epitope specificity curated in the Immune Epitope Database (IEDB) since 2004. We compared seven metrics of sequence similarity to determine their power to predict if two TCRs have the same epitope specificity. We found that a comprehensive k-mer matching approach produced the best results, which we have implemented into TCRMatch, an openly accessible tool (http://tools.iedb.org/tcrmatch/) that takes TCR β-chain CDR3 sequences as an input, identifies TCRs with a match in the IEDB, and reports the specificity of each match. We anticipate that this tool will provide new insights into T cell responses captured in receptor repertoire and single cell sequencing experiments and will facilitate the development of new strategies for monitoring and treatment of infectious, allergic, and autoimmune diseases, as well as cancer.

scholarly journals TCRMatch: Predicting T-cell receptor specificity based on sequence similarity to previously characterized receptors

2020 ◽  
Author(s):  
William D Chronister ◽  
Austin Crinklaw ◽  
Swapnil Mahajan ◽  
Randi Vita ◽  
Zeynep Kosaloglu-Yalcin ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
High Throughput Sequencing ◽  
Sequence Similarity ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
Epitope Specificity ◽  
Receptor Repertoire ◽  
Tcr Repertoire ◽  
Specific Receptors

The adaptive immune system in vertebrates has evolved to recognize non-self-antigens, such as proteins expressed by infectious agents and mutated cancer cells. T cells play an important role in antigen recognition by expressing a diverse repertoire of antigen-specific receptors, which bind epitopes to mount targeted immune responses. Recent advances in high-throughput sequencing have enabled the routine generation of T-cell receptor (TCR) repertoire data. Identifying the specific epitopes targeted by different TCRs in these data would be valuable. To accomplish that, we took advantage of the ever-increasing number of TCRs with known epitope specificity curated in the Immune Epitope Database (IEDB) since 2004. We compared six metrics of sequence similarity to determine their power to predict if two TCRs have the same epitope specificity. We found that a comprehensive k-mer matching approach produced the best results, which we have implemented into TCRMatch, an openly accessible tool (http://tools.iedb.org/tcrmatch/) that takes TCR β-chain CDR3 sequences as an input, identifies TCRs with a match in the IEDB, and reports the specificity of each match. We anticipate that this tool will provide new insights into T cell responses captured in receptor repertoire and single cell sequencing experiments and will facilitate the development of new strategies for monitoring and treatment of infectious, allergic, and autoimmune diseases, as well as cancer.

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 Age-Related Immune Profile of the T Cell Receptor Repertoire, Thymic Recent Output Function, and miRNAs

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yan Xu ◽  
Ling Xu ◽  
Cunte Chen ◽  
Yikai Zhang ◽  
Chengwu Zeng ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Sharp Decrease ◽  
Cell Receptor ◽  
Cell Immune Response ◽  
Immune Senescence ◽  
Receptor Repertoire ◽  
Age Related ◽  
Cell Immunity ◽  
Group I

Background. T cell immunity plays a central role in the body’s defense system, including maintaining homeostasis and preventing tumorigenesis and viral infection. Immune system functions degenerate with age, leading to immune senescence. Physiologically, immune senescence is characterized by a decrease in T cell receptor diversity, naive T cell deficiency, and alterations in T cell immune-related miRNAs. However, little is known about the characteristics of T cell immunosenescence in Chinese individuals. Results. A significant decrease in the miR-17, miR-92a, and miR-181a levels in PBMCs was detected with age. The miR-92a and miR-181a levels were upregulated in CBMCs when comparing healthy individuals to group I (0~9 years), whereas miR-17 was downregulated. The sjTREC level in PBMCs was negatively correlated with age, and a sharp decrease in sjTRECs was found between groups I and II (10~19 years). Twenty-four TCR Vβ subfamilies could be detected in most samples, and most displayed polyclonality, while skewed expression of the Vβ subfamilies as well as an increased oligoclonal tendency was found with age. Similarly, the frequencies of the TCR Vγ and Vδ subfamilies decreased with age, and the alteration in clonality appeared to be stable at different ages. Conclusion. We made the novel observation of T cell immunosenescence with age in Chinese individuals, which may provide information for immune targets to enhance the T cell immune response in immunotherapy settings for elderly patients.

Skewed T-cell receptor repertoire in genetically identical twins correlates with multiple sclerosis

Nature ◽  
1993 ◽  
Vol 364 (6434) ◽  
pp. 243-247 ◽  
Author(s):  
Ursula Utz ◽  
William E. Biddison ◽  
Henry F. McFarland ◽  
Dale E. McFarlin ◽  
Marjorie Flerlage ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Identical Twins ◽  
Receptor Repertoire ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

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
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