ArticleNature2017
Identifying specificity groups in the T cell receptor repertoire.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 647 papers.
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Who cites it
647 citing papers in PubMed, 1,063 citations in OpenAlex.
- Continuous replenishment of the dysfunctional CD8 T cell axis is associated with response to chemoimmunotherapy in advanced breast cancer.Cell reports. Medicine · 2025Trial
- Toward next-generation therapeutic HPV vaccines: A review on expanding the antigen repertoire and an integrated bioinformatics selection framework.Human vaccines & immunotherapeutics · 2026Review
- Heart-specific T cell responses: from antigens to disease mechanisms.Nature reviews. Cardiology · 2026Review
- Cytomegalovirus Latency Fuels Inflammation Following Myocardial Infarction.Circulation research · 2026Article
- T cell immunomonitoring: a comparative analysis of traditional and novel methods to quantify and characterize human antigen-specific T cells.Nature protocols · 2026Review
- Entering the Age of Specificity in T Cell Immunity.Immunological reviews · 2026Review
- Towards high-quality large-scale T cell receptor antigen specificity data: challenges and promises.Nature methods · 2026Article
- How compartmentalization and proliferation shape the splenic T cell repertoire during an immune response to a complex antigen in mice.PLoS computational biology · 2026Article
- Cross-species molecular stratification enables T cell receptor diagnosis of Parkinson's disease.Genome medicine · 2026Article
- Human memory CD4bioRxiv : the preprint server for biology · 2026Article
- Single-cell immune repertoire atlas maps coordinated circulating adaptive immune states in inflammatory bowel disease.bioRxiv : the preprint server for biology · 2026Article
- Single-cell RNA sequencing reveals clonally expanded CD4+ tissue-resident memory T cells in histidyl-tRNA synthetase-induced myositis.JCI insight · 2026Article
- Current landscape and future directions of neoantigen vaccines: A new era of personalized cancer immunotherapy.Innovation (Cambridge (Mass.)) · 2026Review
- Unsupervised identification of low-frequency antigen-specific TCRs using distance-based anomaly scoring.Briefings in bioinformatics · 2026Article
- UcTCRp: a TCRβ-based framework for identifying and profiling MAIT- and iNKT-associated repertoire signals.Briefings in bioinformatics · 2026Article
- Structural T-Cell Receptor Analysis in the Age of Machine Learning.Immunological reviews · 2026Review
- TransTCR: Integrating TCRs and Transcriptomes Through Optimal Transport for Antigen Specificity Prediction.Interdisciplinary sciences, computational life sciences · 2026Article
- Shared CD4+ T cell receptor specificity groups in Crohn's disease and ulcerative colitis.JCI insight · 2026Article
- TSTScope Unifies Single-Cell Multi-Omics to Identify Functional T Cell States Predictive of Immunotherapy Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dynamics of Myelin-Specific T-Cell Repertoires Mirror Disease Activity and Central Nervous System Trafficking in Multiple Sclerosis.International journal of molecular sciences · 2026Article
587 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
T cell receptor (TCR) sequences are very diverse, with many more possible sequence combinations than T cells in any one individual. Here we define the minimal requirements for TCR antigen specificity, through an analysis of TCR sequences using a panel of peptide and major histocompatibility complex (pMHC)-tetramer-sorted cells and structural data. From this analysis we developed an algorithm that we term GLIPH (grouping of lymphocyte interactions by paratope hotspots) to cluster TCRs with a high probability of sharing specificity owing to both conserved motifs and global similarity of complementarity-determining region 3 (CDR3) sequences. We show that GLIPH can reliably group TCRs of common specificity from different donors, and that conserved CDR3 motifs help to define the TCR clusters that are often contact points with the antigenic peptides. As an independent validation, we analysed 5,711 TCRβ chain sequences from reactive CD4 T cells from 22 individuals with latent Mycobacterium tuberculosis infection. We found 141 TCR specificity groups, including 16 distinct groups containing TCRs from multiple individuals. These TCR groups typically shared HLA alleles, allowing prediction of the likely HLA restriction, and a large number of M. tuberculosis T cell epitopes enabled us to identify pMHC ligands for all five of the groups tested. Mutagenesis and de novo TCR design confirmed that the GLIPH-identified motifs were critical and sufficient for shared-antigen recognition. Thus the GLIPH algorithm can analyse large numbers of TCR sequences and define TCR specificity groups shared by TCRs and individuals, which should greatly accelerate the analysis of T cell responses and expedite the identification of specific ligands.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.