ArticleThe Journal of experimental medicine2013
MHC II tetramers visualize human CD4+ T cell responses to Epstein-Barr virus infection and demonstrate atypical kinetics of the nuclear antigen EBNA1 response.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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Who cites it
64 citing papers in PubMed, 121 citations in OpenAlex.
- Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children.PLoS pathogens · 2015Trial
- A tonsil organoid model reveals Epstein-Barr virus-infected germinal center B cell states during primary infection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- LANA-specific CD4Nature communications · 2025Article
- Th1-poised naive CD4 T cell subpopulation reflects anti-tumor immunity and autoimmune disease.Nature communications · 2025Article
- Immunogenetic Profile Associated with Patients Living with HIV-1 and Epstein-Barr Virus (EBV) in the Brazilian Amazon Region.Viruses · 2024Article
- Evaluation of novel Epstein-Barr virus-derived antigen formulations for monitoring virus-specific T cells in pediatric patients with infectious mononucleosis.Virology journal · 2024Article
- Preservation of naive-phenotype CD4+ T cells after vaccination contributes to durable immunity.JCI insight · 2024Article
- Heightened Epstein-Barr virus immunity and potential cross-reactivities in multiple sclerosis.PLoS pathogens · 2024Article
- Differentiation marker-negative CD4bioRxiv : the preprint server for biology · 2024Article
- Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry.Frontiers in immunology · 2024Article
- Cytokine Storm Syndromes Associated with Epstein-Barr Virus.Advances in experimental medicine and biology · 2024Review
- Article
- Concordance of adenosine deaminase with immunoglobulins and lymphocyte subsets in EBV-related diseases.Italian journal of pediatrics · 2023Article
- Mimicking the brain: Epstein-Barr virus and foreign agents as drivers of neuroimmune attack in multiple sclerosis.Frontiers in immunology · 2023Review
- Epstein-Barr virus and multiple sclerosis: moving from questions of association to questions of mechanism.Clinical & translational immunology · 2023Review
- Review
- Targeted delivery of a vaccine protein to Langerhans cells in the human skin via the C-type lectin receptor Langerin.European journal of immunology · 2022Article
- Establishment and recall of SARS-CoV-2 spike epitope-specific CD4Nature immunology · 2022Article
- Preservation of antigen-specific responses in cryopreserved CD4Journal of translational autoimmunity · 2022Article
- CMV exposure drives long-term CD57+ CD4 memory T-cell inflation following allogeneic stem cell transplant.Blood · 2021Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Virus-specific CD4(+) T cells are key orchestrators of host responses to viral infection yet, compared with their CD8(+) T cell counterparts, remain poorly characterized at the single cell level. Here we use nine MHC II-epitope peptide tetramers to visualize human CD4(+) T cell responses to Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis (IM), a disease associated with large virus-specific CD8(+) T cell responses. We find that, while not approaching virus-specific CD8(+) T cell expansions in magnitude, activated CD4(+) T cells specific for epitopes in the latent antigen EBNA2 and four lytic cycle antigens are detected at high frequencies in acute IM blood. They then fall rapidly to values typical of life-long virus carriage where most tetramer-positive cells display conventional memory markers but some, unexpectedly, revert to a naive-like phenotype. In contrast CD4(+) T cell responses to EBNA1 epitopes are greatly delayed in IM patients, in line with the well-known but hitherto unexplained delay in EBNA1 IgG antibody responses. We present evidence from an in vitro system that may explain these unusual kinetics. Unlike other EBNAs and lytic cycle proteins, EBNA1 is not naturally released from EBV-infected cells as a source of antigen for CD4(+) T cell priming.
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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.