Restricted Clonality and Limited Germinal Center Reentry Characterize Memory B Cell Reactivation by Boosting

Cell, Journal Year: 2019, Volume and Issue: 180(1), P. 92 - 106.e11

Published: Dec. 19, 2019

Repeated exposure to pathogens or their antigens triggers anamnestic antibody responses that are higher in magnitude and affinity than the primary response. These involve reengagement of memory B cell (MBC) clones, diversity specificity which determine breadth effectiveness ensuing Using prime-boost models mice, we find secondary characterized by a clonality bottleneck restricts engagement large MBC clones generated priming. Rediversification mutated MBCs is infrequent within germinal centers (GCs), instead consist predominantly cells without prior GC experience detectable clonal expansion. Few generally derived from higher-affinity germline precursors, account for majority responses, while most primary-derived not reengaged detectably boosting. Understanding how counter this may improve our ability elicit antibodies non-immunodominant epitopes vaccination.

Language: Английский

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Overview of methodologies for T-cell receptor repertoire analysis

BMC Biotechnology, Journal Year: 2017, Volume and Issue: 17(1)

Published: July 10, 2017

The T-cell receptor (TCR), located on the surface of T cells, is responsible for recognition antigen-major histocompatibility complex, leading to initiation an inflammatory response. Analysing TCR repertoire may help gain a better understanding immune system features and aetiology progression diseases, in particular those with unknown antigenic triggers. extreme diversity represents major analytical challenge; this has led development specialized methods which aim characterize in-depth. Currently, next generation sequencing based technologies are most widely employed high-throughput analysis cell repertoire.Here, we report latest methodological advancements field by describing comparing available tools; from choice starting material library preparation method, data analysis. Finally, provide practical example our own experience reporting some exemplary results small internal benchmark study, where current approaches literature market compared.Several valid clonotype identification exist, however, gold standard method not yet been identified. Depending purpose scientific be more suitable than others. due possible specific biases, scientists must careful when obtained using different methods.

Language: Английский

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Molecular signatures of antitumor neoantigen-reactive T cells from metastatic human cancers

Science, Journal Year: 2022, Volume and Issue: 375(6583), P. 877 - 884

Published: Feb. 24, 2022

The accurate identification of antitumor T cell receptors (TCRs) represents a major challenge for the engineering cell-based cancer immunotherapies. By mapping 55 neoantigen-specific TCR clonotypes (NeoTCRs) from 10 metastatic human tumors to their single-cell transcriptomes, we identified signatures CD8

Language: Английский

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Computational genomics tools for dissecting tumour–immune cell interactions

Nature Reviews Genetics, Journal Year: 2016, Volume and Issue: 17(8), P. 441 - 458

Published: July 4, 2016

Language: Английский

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Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes

Cell, Journal Year: 2017, Volume and Issue: 172(3), P. 549 - 563.e16

Published: Dec. 21, 2017

Highlights•Development of a human leukocyte antigen library for TCR ligand identification•Single-cell sequencing and phenotyping T cells infiltrating colon cancer•Ligand discovery four tumor-derived cell receptors•Identification shared non-mutated tumor between two patientsSummaryThe immune system can mount responses against tumors; however, the specificities tumor-infiltrating lymphocytes (TILs) are not well understood. We used yeast-display libraries peptide-human (pHLA) to screen antigens "orphan" receptors (TCRs) expressed on TILs from colorectal adenocarcinoma. Four TIL-derived TCRs exhibited strong selection peptides presented in highly diverse pHLA-A∗02:01 library. Three TIL were specific self-antigens, which present separate patient tumors, specificity self-antigen derived U2AF2. These results show that exposed recognition surface MHC-bound accessible contains sufficient structural information enable reconstruction sequences peptide targets pathogenic unknown specificity. This finding underscores surprising their cognate enables facile indentification through unbiased screening.Graphical abstract

Language: Английский

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