Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: April 14, 2020

Abstract Naïve CD4 + T cells coordinate the immune response by acquiring an effector phenotype in to cytokines. However, cytokine responses memory remain largely understudied. Here we use quantitative proteomics, bulk RNA-seq, and single-cell RNA-seq of over 40,000 human naïve show that cytokines differ substantially between these cell types. Memory are unable differentiate into Th2 phenotype, acquire a Th17-like iTreg polarization. Single-cell analyses constitute transcriptional continuum progresses from central cells, forming effectorness gradient accompanied increase expression chemokines Finally, activation influenced gradient. Our results illustrate heterogeneity responses, furthering our understanding inflammation.

Language: Английский

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Understanding the drivers of MHC restriction of T cell receptors

Nature reviews. Immunology, Journal Year: 2018, Volume and Issue: 18(7), P. 467 - 478

Published: April 10, 2018

Language: Английский

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T Cell Epitope Predictions

Annual Review of Immunology, Journal Year: 2020, Volume and Issue: 38(1), P. 123 - 145

Published: Feb. 11, 2020

Throughout the body, T cells monitor MHC-bound ligands expressed on surface of essentially all cell types. MHC that trigger a immune response are referred to as epitopes. Identifying such epitopes enables tracking, phenotyping, and stimulating involved in responses infectious disease, allergy, autoimmunity, transplantation, cancer. The specific recognized an individual determined by genetic factors molecules expresses, parallel individual's environmental exposure history. complexity importance epitope mapping have motivated development computational approaches predict what likely be given or broader population. Such predictions guide experimental studies enable analysis immunogenic potential protein sequence region.

Language: Английский

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Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: Aug. 4, 2020

T cells are involved in the early identification and clearance of viral infections also support development antibodies by B cells. This central role for makes them a desirable target assessing immune response to SARS-CoV-2 infection. Here, we combined two high-throughput profiling methods create quantitative picture T-cell SARS-CoV-2. First, at individual level, deeply characterized 3 acutely infected 58 recovered COVID-19 subjects experimentally mapping their CD8 through antigen stimulation 545 Human Leukocyte Antigen (HLA) class I presented peptides (class II data forthcoming study). Then, population performed repertoire sequencing on 1,815 samples (from 1,521 subjects) as well 3,500 controls identify shared "public" receptors (TCRs) associated with infection from both CD4 Collectively, our reveal that responses often driven few immunodominant, HLA-restricted epitopes. As expected, peaks about one weeks after is detectable least several months recovery. an application these data, trained classifier diagnose based solely TCR blood samples, observed, 99.8% specificity, high sensitivity soon diagnosis (Day 3-7 = 85.1% [95% CI 79.9-89.7]; Day 8-14 94.8% [90.7-98.4]) lasting recovery 29+/convalescent 95.4% [92.1-98.3]). These results demonstrate approach reliably assess adaptive antigenic exposure (before typically detectable) later time points. blood-based molecular characterizing cellular has applications clinical diagnostics vaccine monitoring.

Language: Английский

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TCR-engineered T cell therapy in solid tumors: State of the art and perspectives

Science Advances, Journal Year: 2023, Volume and Issue: 9(7)

Published: Feb. 15, 2023

T cell engineering has changed the landscape of cancer immunotherapy. Chimeric antigen receptor cells have demonstrated a remarkable efficacy in treatment B malignancies hematology. However, their clinical impact on solid tumors been modest so far. expressing an engineered (TCR-T cells) represent promising therapeutic alternative. The target repertoire is not limited to membrane proteins, and intrinsic features TCRs such as high sensitivity near-to-physiological signaling may improve tumor detection killing while improving persistence. In this review, we present results obtained with TCR-T targeting different families. We detail methods that developed identify optimize TCR candidate. also discuss challenges therapies, including toxicity assessment resistance mechanisms. Last, share some perspectives highlight future directions field.

Language: Английский

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