ArticlePLoS pathogens2019
CDR3α drives selection of the immunodominant Epstein Barr virus (EBV) BRLF1-specific CD8 T cell receptor repertoire in primary infection.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Advances in Single-Cell Sequencing for Infectious Diseases: Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Investigation of Long-Term CD4+ T Cell Receptor Repertoire Changes Following SARS-CoV-2 Infection in Patients with Different Severities of Disease.Diagnostics (Basel, Switzerland) · 2024Article
- CD4Oncoimmunology · 2024Article
- T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy.International journal of molecular sciences · 2023Review
- BERTrand-peptide:TCR binding prediction using Bidirectional Encoder Representations from Transformers augmented with random TCR pairing.Bioinformatics (Oxford, England) · 2023Article
- Charge-based interactions through peptide position 4 drive diversity of antigen presentation by human leukocyte antigen class I molecules.PNAS nexus · 2022Article
- Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis.Genes · 2022Article
- Abacavir inhibits but does not cause self-reactivity to HLA-B*57:01-restricted EBV specific T cell receptors.Communications biology · 2022Article
- Cross-reactivity influences changes in human influenza A virus and Epstein Barr virus specific CD8 memory T cell receptor alpha and beta repertoires between young and old.Frontiers in immunology · 2022Article
- Public T-Cell Receptors (TCRs) Revisited by Analysis of the Magnitude of Identical and Highly-Similar TCRs in Virus-Specific T-Cell Repertoires of Healthy Individuals.Frontiers in immunology · 2022Article
- SwarmTCR: a computational approach to predict the specificity of T cell receptors.BMC bioinformatics · 2021Article
- A framework for highly multiplexed dextramer mapping and prediction of T cell receptor sequences to antigen specificity.Science advances · 2021Article
- Intratumoral T-cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B-cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R-CHOP) chemoimmunotherapy.Clinical & translational immunology · 2021Article
- Contribution of T Cell Receptor Alpha and Beta CDR3, MHC Typing, V and J Genes to Peptide Binding Prediction.Frontiers in immunology · 2021Article
- Markov state modeling reveals alternative unbinding pathways for peptide-MHC complexes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Predicting Cross-Reactivity and Antigen Specificity of T Cell Receptors.Frontiers in immunology · 2020Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The T cell receptor (TCR) repertoire is an essential component of the CD8 T-cell immune response. Here, we seek to investigate factors that drive selection of TCR repertoires specific to the HLA-A2-restricted immunodominant epitope BRLF1109-117 (YVLDHLIVV) over the course of primary Epstein Barr virus (EBV) infection. Using single-cell paired TCRαβ sequencing of tetramer sorted CD8 T cells ex vivo, we show at the clonal level that recognition of the HLA-A2-restricted BRLF1 (YVL-BR, BRLF-1109) epitope is mainly driven by the TCRα chain. For the first time, we identify a CDR3α (complementarity determining region 3 α) motif, KDTDKL, resulting from an obligate AV8.1-AJ34 pairing that was shared by all four individuals studied. This observation coupled with the fact that this public AV8.1-KDTDKL-AJ34 TCR pairs with multiple different TCRβ chains within the same donor (median 4; range: 1-9), suggests that there are some unique structural features of the interaction between the YVL-BR/MHC and the AV8.1-KDTDKL-AJ34 TCR that leads to this high level of selection. Newly developed TCR motif algorithms identified a lysine at position 1 of the CDR3α motif that is highly conserved and likely important for antigen recognition. Crystal structure analysis of the YVL-BR/HLA-A2 complex revealed that the MHC-bound peptide bulges at position 4, exposing a negatively charged aspartic acid that may interact with the positively charged lysine of CDR3α. TCR cloning and site-directed mutagenesis of the CDR3α lysine ablated YVL-BR-tetramer staining and substantially reduced CD69 upregulation on TCR mutant-transduced cells following antigen-specific stimulation. Reduced activation of T cells expressing this CDR3 motif was also observed following exposure to mutated (D4A) peptide. In summary, we show that a highly public TCR repertoire to an immunodominant epitope of a common human virus is almost completely selected on the basis of CDR3α and provide a likely structural basis for the selection. These studies emphasize the importance of examining TCRα, as well as TCRβ, in understanding the CD8 T cell receptor repertoire.
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