Evolution of the antigen-specific CD8 + TCR repertoire across the life span: evidence for clonal homogenization of the old TCR repertoire. Epitope-specific TCRβ repertoire diversity imparts no functional advantage on the CD8 + T cell response to cognate viral peptides. The structural dynamics and energetics of an immunodominant T cell receptor are programmed by its Vβ domain. A structural basis for immunodominant human T cell receptor recognition. Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein–Barr virus. Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8 + T-cell responses. Tracking global changes induced in the CD4 T-cell receptor repertoire by immunization with a complex antigen using short stretches of CDR3 protein sequence. Feature selection using a one dimensional naive Bayes’ classifier increases the accuracy of support vector machine classification of CDR3 repertoires. High-throughput pairing of T cell receptor α and β sequences. Chromatin conformation governs T-cell receptor Jβ gene segment usage. High-resolution analysis of the human T-cell receptor repertoire. Highly diverse TCRα chain repertoire of pre-immune CD8 + T cells reveals new insights in gene recombination. Sharing of T cell receptors in antigen-specific responses is driven by convergent recombination. Recombinatorial biases and convergent recombination determine interindividual TCRβ sharing in murine thymocytes. Structural determinants of T-cell receptor bias in immunity. RTCR: a pipeline for complete and accurate recovery of T cell repertoires from high throughput sequencing data. MiTCR: software for T-cell receptor sequencing data analysis. IMGT/HighV-QUEST: the IMGT® web portal for immunoglobulin (IG) or antibody and T cell receptor (TR) analysis from NGS high throughput and deep sequencing. Fast multiclonal clusterization of V(D)J recombinations from high-throughput sequencing. Quantifying lymphocyte receptor diversity. T-cell antigen receptor genes and T-cell recognition. These analyses provide insights into the generalizable, underlying features of epitope-specific repertoires and adaptive immune recognition.ĭavis, M. By identifying shared motifs in core sequences, we were able to highlight key conserved residues driving essential elements of TCR recognition. Our analyses demonstrate that each epitope-specific repertoire contains a clustered group of receptors that share core sequence similarities, together with a dispersed set of diverse ‘outlier’ sequences. We developed analytical tools to characterize these epitope-specific repertoires: a distance measure on the space of TCRs that permits clustering and visualization, a robust repertoire diversity metric that accommodates the low number of paired public receptors observed when compared to single-chain analyses, and a distance-based classifier that can assign previously unobserved TCRs to characterized repertoires with robust sensitivity and specificity. Here we report the in-depth characterization of ten epitope-specific TCR repertoires of CD8 + T cells from mice and humans, representing over 4,600 in-frame single-cell-derived TCRαβ sequence pairs from 110 subjects. Despite this potential diversity, TCRs from T cells that recognize the same pMHC epitope often share conserved sequence features, suggesting that it may be possible to predictively model epitope specificity. TCRs are generated by genomic rearrangement of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate marked diversity of TCRs (estimated to range from 10 15 (ref. T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs).
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