Genetic Bias, Diversity Indices, Physiochemical Properties and CDR3 Motifs Divide Auto-Reactive from Allo-Reactive T-Cell Repertoires

Haigh, Oscar; Grant, Emma J.; Nguyen, Thi H. O.; Kedzierska, Katherine; Field, Matthew A.; Miles, John J.

doi:10.3390/ijms22041625

Cited by 4 publications

(2 citation statements)

References 63 publications

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“…Furthermore, the comparison of TCRs in different T cell subpopulations would reveal important insights into the T cell subset function, that are occluded in bulk TCR analysis. FACS sorting combined with deep TCR sequencing could enrich T cells from tissue samples or directly obtain certain T cell subgroups to facilitate more comprehensive and detailed TCR analysis (102)(103)(104). According to specific surface markers or dye, FACS sorting can also be applied to isolate alloreactive T cell subsets with cytotoxic function and particular cytokine production patterns (Figure 2B) (82,105,106).…”

Section: High-throughput Technology Revolutionized Methods For Measuring Alloresponsementioning

confidence: 99%

Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

Tian

2022

Front. Immunol.

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T cells play a key role in determining allograft function by mediating allogeneic immune responses to cause rejection, and recent work pointed their role in mediating tolerance in transplantation. The unique T-cell receptor (TCR) expressed on the surface of each T cell determines the antigen specificity of the cell and can be the specific fingerprint for identifying and monitoring. Next-generation sequencing (NGS) techniques provide powerful tools for deep and high-throughput TCR profiling, and facilitate to depict the entire T cell repertoire profile and trace antigen-specific T cells in circulation and local tissues. Tailing T cell transcriptomes and TCR sequences at the single cell level provides a full landscape of alloreactive T-cell clones development and biofunction in alloresponse. Here, we review the recent advances in TCR sequencing techniques and computational tools, as well as the recent discovery in overall TCR profile and antigen-specific T cells tracking in transplantation. We further discuss the challenges and potential of using TCR sequencing-based assays to profile alloreactive TCR repertoire as the fingerprint for immune monitoring and prediction of rejection and tolerance.

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Section: High-throughput Technology Revolutionized Methods For Measuring Alloresponsementioning

confidence: 99%

Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

Tian

2022

Front. Immunol.

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“…The R package sumrep [20] provides functions to compare the CDR3 properties of two repertoires, such as the CDR3 length and a number of amino acid physicochemical properties [31,32].…”

Section: Properties Of the Cdr3mentioning

confidence: 99%

Adaptive Immune Receptor Repertoire (AIRR) Community Guide to Repertoire Analysis

Marquez

Babrak

Greiff

et al. 2022

Methods in Molecular Biology

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Adaptive immune receptor repertoires (AIRRs) are rich with information that can be mined for insights into the workings of the immune system. Gene usage, CDR3 properties, clonal lineage structure, and sequence diversity are all capable of revealing the dynamic immune response to perturbation by disease, vaccination, or other interventions. Here we focus on a conceptual introduction to the many aspects of repertoire analysis and orient the reader toward the uses and advantages of each. Along the way, we note some of the many software tools that have been developed for these investigations and link the ideas discussed to chapters on methods provided elsewhere in this volume.

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The characteristics of T‐cell receptor repertoire in relation to systemic immune response of patients with ischemic stroke

Zong,

Liu,

Wang

et al. 2024

Journal of Neurochemistry

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T lymphocytes play a vital role in the immune‐inflammatory response following a stroke. However, the specific mechanisms behind the contrasting functions of T cells in the brain and peripheral tissues after a stroke remain unclear and require further investigation. T‐cell receptors (TCRs) are essential in controlling how T lymphocytes develop and become active. This study aims to gain a deeper understanding of the biological function of T lymphocytes by analyzing the TCR repertoire in patients who have experienced an acute ischemic stroke (AIS). High‐throughput TCR sequencing was conducted on peripheral blood samples from 25 AIS patients and 10 healthy controls. We compared the percentage of T cells and the characteristics of the TCR repertoire, specifically focusing on the recombination of V(D)J gene fragments and the diversity of the complementarity determining region 3 (CDR3) of the Vβ gene. Additionally, this study analyzed the potential biological significance of the skewed TCR repertoire in AIS patients. In patients with AIS, the proportion of circulating lymphocytes (LY%) decreased while the systemic immune‐inflammatory index (SII) increased compared to healthy controls. The average number of TCR read pairs decreased, corresponding with the presence of lymphopenia. However, the recombination of V(D)J gene fragments, the number of CDR3 clonotypes, and the diversity of CDR3 was elevated in the peripheral blood of AIS patients. Furthermore, the increased number of CDR3 amino acid or nucleotide clonotypes was negatively correlated with neurologic deficits but positively correlated with AIS patients' systemic immune condition and functional outcomes. Our findings suggest that both immunosuppression and enhanced antigen‐specific T‐cell response may exist in the periphery of the AIS patients. Further investigation into the mechanisms underlying these opposing changes may lead to the discovery of novel targets to reverse immunosuppression or mitigate the detrimental effects of T cells in the lesioned brain of AIS patients.image

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Genetic Bias, Diversity Indices, Physiochemical Properties and CDR3 Motifs Divide Auto-Reactive from Allo-Reactive T-Cell Repertoires

Cited by 4 publications

References 63 publications

Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

Adaptive Immune Receptor Repertoire (AIRR) Community Guide to Repertoire Analysis

The characteristics of T‐cell receptor repertoire in relation to systemic immune response of patients with ischemic stroke

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