68,257 results match your criteria t-cell receptor

Single Molecule Force Spectroscopy Reveals Distinctions in Key Biophysical Parameters of αβ T-Cell Receptors Compared with Chimeric Antigen Receptors Directed at the Same Ligand.

J Phys Chem Lett 2021 Aug 4:7566-7573. Epub 2021 Aug 4.

Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States.

Chimeric antigen receptor (CAR) T-cell therapies exploit facile antibody-mediated targeting to elicit useful immune responses in patients. This work directly compares binding profiles of CAR and αβ T-cell receptors (TCR) with single cell and single molecule optical trap measurements against a shared ligand. DNA-tethered measurements of peptide-major histocompatibility complex (pMHC) ligand interaction in both CAR and TCR exhibit catch bonds with specific peptide agonist peaking at 25 and 14 pN, respectively. Read More

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Turn-key mapping of cell receptor force orientation and magnitude using a commercial structured illumination microscope.

Nat Commun 2021 Aug 3;12(1):4693. Epub 2021 Aug 3.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.

Many cellular processes, including cell division, development, and cell migration require spatially and temporally coordinated forces transduced by cell-surface receptors. Nucleic acid-based molecular tension probes allow one to visualize the piconewton (pN) forces applied by these receptors. Building on this technology, we recently developed molecular force microscopy (MFM) which uses fluorescence polarization to map receptor force orientation with diffraction-limited resolution (~250 nm). Read More

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Chimeric non-antigen receptors in T cell-based cancer therapy.

J Immunother Cancer 2021 Aug;9(8)

Division of Medical Oncology, Department of Medicine, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, USA

Adoptively transferred T cell-based cancer therapies have shown incredible promise in treatment of various cancers. So far therapeutic strategies using T cells have focused on manipulation of the antigen-recognition machinery itself, such as through selective expression of tumor-antigen specific T cell receptors or engineered antigen-recognition chimeric antigen receptors (CARs). While several CARs have been approved for treatment of hematopoietic malignancies, this kind of therapy has been less successful in the treatment of solid tumors, in part due to lack of suitable tumor-specific targets, the immunosuppressive tumor microenvironment, and the inability of adoptively transferred cells to maintain their therapeutic potentials. Read More

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Assessment of Clonotypic Rearrangements and Minimal Residual Disease in Lymphoid Malignancies: A Large Cancer Center Experience Using clonoSEQ.

Arch Pathol Lab Med 2021 Aug 3. Epub 2021 Aug 3.

Malignant Hematology (Shah, Pinilla-Ibarz, Shain), Moffitt Cancer Center, Tampa, Florida.

Context.—: Measurable (minimal) residual disease (MRD) is an independent prognostic factor for survival outcomes in patients with lymphoid and plasma cell malignancies and has been incorporated into consensus criteria regarding treatment response, strategy, and clinical trial endpoints. clonoSEQ (a next-generation sequencing [NGS]-MRD assay) uses multiplex polymerase chain reaction and NGS to identify clonotypic rearrangements at the immunoglobulin (Ig) H, IgK, IgL, T-cell receptor (TCR)-β, and TCR-γ loci, and translocated B-cell lymphoma 1/IgH and 2/IgH sequences for MRD assessment. Read More

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Using de novo assembly to identify structural variation of eight complex immune system gene regions.

PLoS Comput Biol 2021 Aug 3;17(8):e1009254. Epub 2021 Aug 3.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

Driven by the necessity to survive environmental pathogens, the human immune system has evolved exceptional diversity and plasticity, to which several factors contribute including inheritable structural polymorphism of the underlying genes. Characterizing this variation is challenging due to the complexity of these loci, which contain extensive regions of paralogy, segmental duplication and high copy-number repeats, but recent progress in long-read sequencing and optical mapping techniques suggests this problem may now be tractable. Here we assess this by using long-read sequencing platforms from PacBio and Oxford Nanopore, supplemented with short-read sequencing and Bionano optical mapping, to sequence DNA extracted from CD14+ monocytes and peripheral blood mononuclear cells from a single European individual identified as HV31. Read More

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A comprehensive model based on temporal dynamics of peripheral T cell repertoire for predicting post-treatment distant metastasis of nasopharyngeal carcinoma.

Cancer Immunol Immunother 2021 Aug 3. Epub 2021 Aug 3.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.

Many nasopharyngeal carcinoma (NPC) patients develop distant metastases after treatment, leading to poor outcomes. To date, there are no peripheral biomarkers suitable for all NPC patients to predict distant metastasis. Hence, we purposed to develop a noninvasive comprehensive model for predicting post-treatment distant metastasis of all NPC. Read More

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Convergent epitope-specific T cell responses after SARS-CoV-2 infection and vaccination.

medRxiv 2021 Jul 27. Epub 2021 Jul 27.

SARS-CoV-2 mRNA vaccines, including Pfizer/Biontech BNT162b2, were shown to be effective for COVID-19 prevention, eliciting both robust antibody responses in naive individuals and boosting pre-existing antibody levels in SARS-CoV-2-recovered individuals. However, the magnitude, repertoire, and phenotype of epitope-specific T cell responses to this vaccine, and the effect of vaccination on pre-existing T cell memory in SARS-CoV-2 convalescent patients, are still poorly understood. Thus, in this study we compared epitope-specific T cells elicited after natural SARS-CoV-2 infection, and vaccination of both naive and recovered individuals. Read More

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Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells.

Front Immunol 2021 14;12:695972. Epub 2021 Jul 14.

Louisiana State University Cancer Center, New Orleans, LA, United States.

COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Read More

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Crosstalk between γδ T cells and the microbiota.

Nat Microbiol 2021 Aug 2. Epub 2021 Aug 2.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.

The role of the microbiota in the development and function of γδ T cells-a T cell subset characterized by a T cell receptor composed of one γ-chain and one δ-chain-has been investigated in multiple organs in mice and humans. Interactions between the microbiota and γδ T cells affect both tissue homeostasis and disease pathologies. Notably, microbiota-induced interleukin-17 (IL-17)-producing-γδ T cells can mediate a range of immunological processes, from metabolic disorders to neuroinflammation via the gut-brain axis. Read More

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Pan-vaccinomics approach towards a universal vaccine candidate against WHO priority pathogens to address growing global antibiotic resistance.

Comput Biol Med 2021 Jul 28;136:104705. Epub 2021 Jul 28.

College of Life Science and Technology, Guangxi University, Nanning, PR China. Electronic address:

Antimicrobial resistance (AMR) in bacterial pathogens is a major global distress. Due to the slow progress of antibiotics development and the fast pace of resistance acquisition, there is an urgent need for effective vaccines against such bacterial pathogens. In-silico approaches including pan-genomics, subtractive proteomics, reverse vaccinology, immunoinformatics, molecular docking, and dynamics simulation studies were applied in the current study to identify a universal potential vaccine candidate against the 18 multi-drug resistance (MDRs) bacterial pathogenic species from a WHO priority list. Read More

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Minimal residual disease (MRD) detection in acute lymphoblastic leukaemia based on fusion genes and genomic deletions: towards MRD for all.

Br J Haematol 2021 Aug 1. Epub 2021 Aug 1.

Department of Immunology, Laboratory Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Minimal residual disease (MRD) diagnostics are implemented in most clinical protocols for patients with acute lymphoblastic leukaemia (ALL) and are mostly performed using rearranged immunoglobulin (IG) and/or T-cell receptor (TR) gene rearrangements as molecular polymerase chain reaction targets. Unfortunately, in 5-10% of patients no or no sensitive IG/TR targets are available, and patients therefore cannot be stratified appropriately. In the present study, we used fusion genes and genomic deletions as alternative MRD targets in these patients, which retrospectively revealed appropriate MDR stratification in 79% of patients with no (sensitive) IG/TR target, and a different risk group stratification in more than half of the cases. Read More

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Genetics of Severe Cutaneous Adverse Reactions.

Front Med (Lausanne) 2021 15;8:652091. Epub 2021 Jul 15.

Department of Dermatology, Xiamen Chang Gung Allergology Consortium, Xiamen Chang Gung Hospital, Xiamen, China.

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) are T cells-mediated life-threatening immune reactions, most commonly induced by drug. The last decade has seen significant progress in SCARs research. Recent studies have unveiled the pathogenesis of SCARs involved in susceptible genes, including human leukocyte antigens (HLA) and drugs-T cell receptor (TCR) interaction that may trigger T cell activation with downstream immune signaling of cytokines/chemokines and specific cytotoxic proteins releases. Read More

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Targeting Neoepitopes to Treat Solid Malignancies: Immunosurgery.

Front Immunol 2021 15;12:592031. Epub 2021 Jul 15.

ImmunoSurgery Unit, Champalimaud Centre for the Unknown, Lisbon, Portugal.

Successful outcome of immune checkpoint blockade in patients with solid cancers is in part associated with a high tumor mutational burden (TMB) and the recognition of private neoantigens by T-cells. The quality and quantity of target recognition is determined by the repertoire of 'neoepitope'-specific T-cell receptors (TCRs) in tumor-infiltrating lymphocytes (TIL), or peripheral T-cells. Interferon gamma (IFN-γ), produced by T-cells and other immune cells, is essential for controlling proliferation of transformed cells, induction of apoptosis and enhancing human leukocyte antigen (HLA) expression, thereby increasing immunogenicity of cancer cells. Read More

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Large-Scale Transcriptome Analysis Identified a Novel Cancer Driver Genes Signature for Predicting the Prognostic of Patients With Hepatocellular Carcinoma.

Front Pharmacol 2021 16;12:638622. Epub 2021 Jul 16.

Second Department of Oncology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and heterogeneity. Genetic mutations caused by driver genes are important contributors to the formation of the tumor microenvironment. The purpose of this study is to discuss the expression of cancer driver genes in tumor tissues and their clinical value in predicting the prognosis of HCC. Read More

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High-affinity T-cell receptor specific for MyD88 L265P mutation for adoptive T-cell therapy of B-cell malignancies.

J Immunother Cancer 2021 Jul;9(7)

Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Background: Adoptive transfer of engineered T cells has shown remarkable success in B-cell malignancies. However, the most common strategy of targeting lineage-specific antigens can lead to undesirable side effects. Also, a substantial fraction of patients have refractory disease. Read More

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Subpopulations of swine γδ T cells defined by TCRγ and WC1 gene expression.

Dev Comp Immunol 2021 Jul 27:104214. Epub 2021 Jul 27.

Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria. Electronic address:

γδ T cells constitute a major portion of lymphocytes in the blood of both ruminants and swine. Subpopulations of swine γδ T cells have been distinguished by CD2 and CD8α expression. However, it was not clear if they have distinct expression profiles of their T-cell receptor (TCR) or WC1 genes. Read More

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Advanced HCC Patient Benefit From Neoantigen Reactive T Cells Based Immunotherapy: A Case Report.

Front Immunol 2021 13;12:685126. Epub 2021 Jul 13.

Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China.

Advanced hepatocellular carcinoma (HCC) is a highly lethal disease, mainly due to the late stage at diagnosis and its rapid progression. Although patients with advanced HCC can choose targeted therapy or chemotherapy, overall, the treatment response rate is extremely low and the average survival time is one year more or less. But the application of immunotherapy have led to a paradigm shift in the treatment of HCC,such as TILs (tumor infiltrating lymphocytes),Checkpoint blockade (immune Checkpoint blockade), CAR-T(chimeric antigen receptor T cells) and TCR-T (engineered t-cell receptor T cells). Read More

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CXCR5CD8 T Cells Shape Antibody Responses Following Protein Immunisation and Peripheral Viral Infection.

Front Immunol 2021 13;12:626199. Epub 2021 Jul 13.

Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.

Crosstalk between T and B cells is crucial for generating high-affinity, class-switched antibody responses. The roles of CD4 T cells in this process have been well-characterised. In contrast, regulation of antibody responses by CD8 T cells is significantly less defined. Read More

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Effector memory CD4T cells in mesenteric lymph nodes mediate bone loss in food-allergic enteropathy model mice, creating IL-4 dominance.

Mucosal Immunol 2021 Jul 29. Epub 2021 Jul 29.

Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Intestinal inflammation can be accompanied by osteoporosis, but their relationship, mediated by immune responses, remains unclear. Here, we investigated a non-IgE-mediated food-allergic enteropathy model of ovalbumin (OVA) 23-3 mice expressing OVA-specific T-cell-receptor transgenes. Mesenteric lymph nodes (MLNs) and their pathogenic CD4T cells were important to enteropathy occurrence and exacerbation when the mice were fed an egg-white (EW) diet. Read More

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Src/lck inhibitor dasatinib reversibly switches off cytokine release and T cell cytotoxicity following stimulation with T cell bispecific antibodies.

J Immunother Cancer 2021 Jul;9(7)

Roche Pharma Research and Early Development, Roche Innovation Centre Zurich, Schlieren, Switzerland.

Background: T cell engagers are bispecific antibodies recognizing, with one moiety, the CD3ε chain of the T cell receptor and, with the other moiety, specific tumor surface antigens. Crosslinking of CD3 upon simultaneous binding to tumor antigens triggers T cell activation, proliferation and cytokine release, leading to tumor cell killing. Treatment with T cell engagers can be associated with safety liabilities due to on-target on-tumor, on-target off-tumor cytotoxic activity and cytokine release syndrome (CRS). Read More

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Comparison of two qPCR-based assays for detection of minimal residual disease in B-precursor acute lymphoblastic leukemia harboring three major fusion transcripts.

J Mol Diagn 2021 Jul 26. Epub 2021 Jul 26.

Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address:

Two quantitative polymerase chain reaction (qPCR) based-methods, for clonal immunoglobulin or T-cell receptor gene (Ig/TCR) rearrangements and for fusion transcripts, are widely used for the measurement of minimal residual disease (MRD) in patients with B-precursor acute lymphoblastic leukemia (B-ALL). MRD of bone marrow samples from 165 patients carrying the 3 major fusion transcripts including 74 BCR-ABL1, 54 ETV6-RUNX1, and 37 TCF3-PBX1 were analyzed by using the 2 qPCR-based methods. The coefficient correlation of both methods was good for TCF3-PBX1 (R = 0. Read More

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Mutant B2M-HLA-E and B2M-HLA-G fusion proteins protects universal chimeric antigen receptor-modified T cells from allogeneic NK cell-mediated lysis.

Eur J Immunol 2021 Jul 29. Epub 2021 Jul 29.

Department of Bio-therapeutic, the First Medical Centre, Chinese PLA General Hospital, Beijing, China.

Recent studies have indicated the anti-tumor activity and reduced allogeneic response of universal chimeric antigen receptor-modified T (UCAR T) cells lacking endogenous T cell receptors and beta-2 microglobulin (B2M) generated using gene-editing technologies. However, these cells are vulnerable to lysis by allogeneic natural killer (NK) cells due to their lack of human leukocyte antigen (HLA) class I molecule expression. Here, constitutive expression of mutant B2M-HLA-E (mBE) and B2M-HLA-G (mBG) fusion proteins in anti-CD19 UCAR T (UCAR T-19) cells was conducted to protect against allogeneic NK cell-mediated lysis. Read More

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Genome-Wide Analysis Identifies and as Novel Notch1 Transcriptional Targets in Thymocytes.

Front Cell Dev Biol 2021 12;9:703338. Epub 2021 Jul 12.

Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Recombination activating genes 1 () and are expressed in immature lymphocytes and essential for generating the vast repertoire of antigen receptors. Yet, the mechanisms governing the transcription of and remain to be fully determined, particularly in thymocytes. Combining cDNA microarray and ChIP-seq analysis, we identify and as novel Notch1 transcriptional targets in acute T-cell lymphoblastic leukemia (T-ALL) cells. Read More

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Chimeric Antigen Receptor T Cell Therapy and Its Significance in Multiple Myeloma.

Cureus 2021 Jun 25;13(6):e15917. Epub 2021 Jun 25.

Internal Medicine, Advent Health & Orlando Health Hospital/JC Medical Center, Orlando, USA.

Multiple myeloma (MM) has a five-year prevalence worldwide of 230,000 people and is known as the second most common hematological malignancy within the United States. Extensive research has been conducted to gain a wide range of treatment strategies, providing hope to these patients. Combination therapy using chemotherapy, monoclonal antibodies, and immunomodulatory drugs are the current management of choice. Read More

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RNA sequencing identifies global transcriptional changes in peripheral CD4 cells during active oesophagitis and following epicutaneous immunotherapy in eosinophilic oesophagitis.

Clin Transl Immunology 2021 22;10(7):e1314. Epub 2021 Jul 22.

Division of Allergy and Immunology The Children's Hospital of Philadelphia Philadelphia PA USA.

Objective: There are no disease-modifying therapies for the treatment of eosinophilic oesophagitis (EoE), which is driven by non-IgE-mediated allergic inflammation. A recent clinical trial of milk epicutaneous immunotherapy (EPIT) has shown initial promise, with 47% of treated EoE patients tolerating milk without recurrence of disease. Mechanisms of EPIT in EoE have not been studied in humans. Read More

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CD8 T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs.

Front Immunol 2021 12;12:690069. Epub 2021 Jul 12.

State Key Laboratory of Animal Nutrition, Ministry of Agriculture Key Laboratory of Animal Genetics Breeding and Reproduction, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.

Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. Read More

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Human immune repertoire in hepatitis B virus infection.

World J Gastroenterol 2021 Jul;27(25):3790-3801

Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.

Hepatitis B virus (HBV) infection is a public health threat that affects 257 million people worldwide and can progress to liver cirrhosis, liver failure, and hepatocellular carcinoma. The HBV antigen- induced adaptive immune response plays an important role in HBV clearance. Immune repertoire sequencing (IRS) has been used to investigate the molecular mechanisms behind the immune system, find novel ways to treat HBV infection, and evaluate the genetic responses and immune characteristics of individuals infected by HBV or immunized by HBV vaccine. Read More

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Direct identification of neoantigen-specific TCRs from tumor specimens by high-throughput single-cell sequencing.

J Immunother Cancer 2021 Jul;9(7)

Surgery Branch, National Institutes of Health, Bethesda, Maryland, USA.

Background: Recognition of neoantigens by T cells plays a major role in cancer immunotherapy. Identification of neoantigen-specific T-cell receptors (TCRs) has become a critical research tool for studying T cell-mediated responses after immunotherapy. In addition, neoantigen-specific TCRs can be used to modify the specificity of T cells for T cell-based therapies targeting tumor-specific mutations. Read More

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A deep insight into CRISPR/Cas9 application in CAR-T cell-based tumor immunotherapies.

Stem Cell Res Ther 2021 07 28;12(1):428. Epub 2021 Jul 28.

Department of Virology, Pasteur Institute of Iran, Tehran, Iran.

To date, two chimeric antigen receptors (CAR)-T cell products from autologous T cells have been approved by The United States Food and Drug Administration (FDA). The case-by-case autologous T cell generation setting is largely considered as a pivotal restraining cause for its large-scale clinical use because of the costly and prolonged manufacturing procedure. Further, activated CAR-T cells mainly express immune checkpoint molecules, including CTLA4, PD1, LAG3, abrogating CAR-T anti-tumor activity. Read More

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iCAT: diagnostic assessment tool of immunological history using high-throughput T-cell receptor sequencing.

F1000Res 2021 3;10:65. Epub 2021 Feb 3.

Program in Bioinformatics and Computational Biology, Saint Louis University, St. Louis, MO, 63103, USA.

The pathogen exposure history of an individual is recorded in their T-cell repertoire and can be accessed through the study of T-cell receptors (TCRs) if the tools to identify them were available. For each T-cell, the TCR loci undergoes genetic rearrangement that creates a unique DNA sequence. In theory these unique sequences can be used as biomarkers for tracking T-cell responses and cataloging immunological history. Read More

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