Bohemian T cell receptors: sketching the repertoires of unconventional lymphocytes

Schattgen, Stefan A.; Thomas, Paul G.

doi:10.1111/imr.12668

Cited by 8 publications

(2 citation statements)

References 84 publications

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“…Turning to the dataset of human CD8+ T cells (Fig. 2f), we again see two MAIT clusters, (4,11) and (4,5), differentiated by their TCR beta chain V gene usage (TRBV20 versus TRBV6). Cluster (2,12) is characterized by a strong TCR beta chain sequence motif and high expression of cytotoxicity/activation markers including GNLY and CCL5.…”

Section: Conga Graph-vs-graph Analysis Identifies Correlation Between...mentioning

confidence: 83%

“…However, the relationship between TCR sequence similarity and cellular phenotype has not, to our knowledge, been systematically explored using the large single-cell datasets now available. Researchers have mapped the TCR sequence properties of previously identified T cell subsets [9][10][11] , but approaches that can identify completely new populations or subpopulations by correlating GEX and TCR sequence have not been reported. Also lacking are methods for identifying correlations between TCR sequence and GEX that do not extend to global similarity or associate with a defined cell population, for example, correlations between specific TCR sequence properties and expressed genes that might span multiple cell subsets.…”

Section: Introductionmentioning

confidence: 99%

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Integrating T cell receptor sequences and transcriptional profiles by clonotype neighbor graph analysis (CoNGA)

et al. 2021

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Multi-modal single-cell technologies capable of simultaneously assaying gene expression and surface phenotype across large numbers of immune cells have described extensive heterogeneity within these complex populations, in healthy and diseased states. In the case of T cells, these technologies have made it possible to profile clonotype, defined by T cell receptor (TCR) sequence, and phenotype, as reflected in gene expression (GEX) profile, surface protein expression, and peptide:MHC (pMHC) binding, across large and diverse cell populations. These rich, high-dimensional datasets have the potential to reveal new relationships between TCR sequence and T cell phenotype that go beyond identification of features shared by clonally related cells. In order to uncover these connections in an unbiased way, we developed a graph-theoretic approach---clonotype neighbor-graph analysis or "CoNGA"---that identifies correlations between GEX profile and TCR sequence through statistical analysis of a pair of T cell similarity graphs, one in which cells are linked based on gene expression similarity and another in which cells are linked by similarity of TCR sequence. Applying CoNGA across diverse human and mouse T cell datasets uncovered known and novel associations between TCR sequence features and cellular phenotype including the classical invariant T cell subsets; a novel defined population of human blood CD8+ T cells expressing the transcription factors HOBIT and HELIOS, NK-associated receptors, and a biased TCR repertoire, representing a potential previously undescribed lineage of "natural lymphocytes"; a striking association between usage of a specific V-beta gene segment and expression of the EPHB6 gene that is conserved between mouse and human; and TCR sequence determinants of differentiation in developing thymocytes. As the size and scale of single-cell datasets continue to grow, we expect that CoNGA will prove to be a useful tool for deconvolving complex relationships between TCR sequence and cellular state in single-cell applications..

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Section: Conga Graph-vs-graph Analysis Identifies Correlation Between...mentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Integrating T cell receptor sequences and transcriptional profiles by clonotype neighbor graph analysis (CoNGA)

et al. 2021

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Single cell transcriptomics reveal the heterogeneities of TCR Vα7.2+CD161+ and TCR Vα7.2+CD161− T cells in human peripheral blood

Li,

Jin,

Wei

et al. 2023

Curr Med

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Purpose T cell receptor (TCR) usually determines the specificity and unique function of T cells. Recently, the unconventional T cells with a unique TCR have attracted great attentions because of their clinical importance. TCR Vα7.2+ cells, that consist of the CD161+ mucosal associated invariant T (MAIT) cells and CD161− non-MAIT T cells, have been reported to play crucial roles in immune defenses. However, their characterizations in human blood are still obscure. This study aims to investigate the signatures and functions of circulating TCR Vα7.2+CD161+ MAIT and TCR Vα7.2+CD161− cells under steady state. Methods The TCR Vα7.2+CD161+ and TCR Vα7.2+CD161− cells were separately sorted from healthy donor peripheral blood mononuclear cells (PBMCs) and send for single cell RNA sequencing (scRNA-seq). Flow cytometry analysis was used to verify the findings obtained from scRNA-seq analysis. Results Our findings demonstrated that there are more TCR Vα7.2+CD161+ cells than TCR Vα7.2+CD161− cells in healthy donor PBMCs and revealed the differences between them. Under steady state, 4 TCR Vα7.2+CD161+ MAIT clusters existed in peripheral blood. Pseudotime analysis further implied the development trajectory of these MAIT cells, which was ordered from CCR7+ resting cluster to LGALS3+ transitional cluster, followed by KLRG1+ cluster and ending with CX3CR1+ terminally differentiated cytotoxic cluster. In addition, our results revealed that TCR Vα7.2+CD161− cells consist of different kind of conventional T cells. These TCR Vα7.2+CD161− non-MAIT cells showed a higher level of Granzyme B expression and upregulated genes associated with cytotoxicity, which implicated their roles in immune defense. Conclusion Our findings advanced the understandings of the evolution of circulating MAIT cells. We also preliminarily defined the TCR Vα7.2+CD161− PBMCs as a combination of versatile CD4+ and CD8+ populations with cytotoxicity.

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Unconventional T cells – New players in antifungal immunity

Dunne

Wagener

Loeffler

et al. 2021

Clinical Immunology

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Bohemian T cell receptors: sketching the repertoires of unconventional lymphocytes

Cited by 8 publications

References 84 publications

Integrating T cell receptor sequences and transcriptional profiles by clonotype neighbor graph analysis (CoNGA)

Integrating T cell receptor sequences and transcriptional profiles by clonotype neighbor graph analysis (CoNGA)

Single cell transcriptomics reveal the heterogeneities of TCR Vα7.2+CD161+ and TCR Vα7.2+CD161− T cells in human peripheral blood

Unconventional T cells – New players in antifungal immunity

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