ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Cytotoxic CD4+ T cell responses to EBV contrast with CD8 responses in breadth of lytic cycle antigen choice and in lytic cycle recognition.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 76 citations in OpenAlex.
- The Cellular Localization of Human Cytomegalovirus Glycoprotein Expression Greatly Influences the Frequency and Functional Phenotype of Specific CD4+ T Cell Responses.Journal of immunology (Baltimore, Md. : 1950) · 2015Trial
- Long-persisting SARS-CoV-2 spike-specific CD4Nature communications · 2025Article
- Research landmarks on the 60th anniversary of Epstein-Barr virus.Science China. Life sciences · 2025Review
- EBV-specific T-cell immunity: relevance for multiple sclerosis.Frontiers in immunology · 2024Review
- Multivalent MVA-vectored vaccine elicits EBV neutralizing antibodies in rhesus macaques that reduce EBV infection in humanized mice.Frontiers in immunology · 2024Article
- Article
- Mechanisms of T cell evasion by Epstein-Barr virus and implications for tumor survival.Frontiers in immunology · 2023Review
- Facts and Hopes in the Relationship of EBV with Cancer Immunity and Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Review
- Concomitant Cytotoxic Effector Differentiation of CD4Cancers · 2022Article
- CD4 + T cells are found within endemic Burkitt lymphoma and modulate Burkitt lymphoma precursor cell viability and expression of pathogenically relevant Epstein-Barr virus genes.Cancer immunology, immunotherapy : CII · 2022Article
- Cytotoxic CD4+ T-cells specific for EBV capsid antigen BORF1 are maintained in long-term latently infected healthy donors.PLoS pathogens · 2021Article
- Review
- Roles of Lytic Viral Replication and Co-Infections in the Oncogenesis and Immune Control of the Epstein-Barr Virus.Cancers · 2021Review
- T cell epitope screening of Epstein-Barr virus fusion protein gB.Journal of virology · 2021Article
- The dominantly expressed class II molecule from a resistant MHC haplotype presents only a few Marek's disease virus peptides by using an unprecedented binding motif.PLoS biology · 2021Article
- PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity.PLoS pathogens · 2021Article
- The Epstein-Barr Virus Major Tegument Protein BNRF1 Is a Common Target of Cytotoxic CD4Journal of virology · 2020Article
- Immunology of EBV-Related Lymphoproliferative Disease in HIV-Positive Individuals.Frontiers in oncology · 2020Review
- Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Progress in EBV Vaccines.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
EBV, a B lymphotropic herpesvirus, encodes two immediate early (IE)-, >30 early (E)-, and >30 late (L)-phase proteins during its replication (lytic) cycle. Despite this, lytic Ag-induced CD8 responses are strongly skewed toward IE and a few E proteins only, all expressed before HLA I presentation is blocked in lytically infected cells. For comparison, we examined CD4(+) T cell responses to eight IE, E, or L proteins, screening 14 virus-immune donors to overlapping peptide pools in IFN-γ ELISPOT assays, and established CD4(+) T cell clones against 12 defined epitopes for target-recognition assays. We found that the lytic Ag-specific CD4(+) T cell response differs radically from its CD8 counterpart in that it is widely distributed across IE, E, and L Ag targets, often with multiple reactivities detectable per donor and with IE, E, or L epitope responses being numerically dominant, and that all CD4(+) T cell clones, whether IE, E, or L epitope-specific, show strong recognition of EBV-transformed B cell lines, despite the lines containing only a small fraction of lytically infected cells. Efficient recognition occurs because lytic Ags are released into the culture and are acquired and processed by neighboring latently infected cells. These findings suggested that lytic Ag-specific CD4 responses are driven by a different route of Ag display than drives CD8 responses and that such CD4 effectors could be therapeutically useful against EBV-driven lymphoproliferative disease lesions, which contain similarly small fractions of EBV-transformed cells entering the lytic cycle.
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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.