ArticleNature medicine2015
Endogenous antigen processing drives the primary CD4+ T cell response to influenza.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 75 citations in OpenAlex.
- Generation and MHC class II loading of an endogenous influenza epitope revealed by a T cell receptor-like antibody.bioRxiv : the preprint server for biology · 2026Article
- Review
- Nasal CD4+ tissue-resident memory T cells provide cross-protective immunity to influenza.The Journal of experimental medicine · 2026Article
- Conditional T and NK cell antagonism by a giant and highly conserved orthopoxvirus virulence factor.Research square · 2026Article
- Optimal murine CD4Nature communications · 2026Article
- Cut or bind? Antigen-specific processing mechanisms define CD4Genome medicine · 2025Article
- Cryptic MHC-E epitope from influenza elicits a potent cytolytic T cell response.Nature immunology · 2023Article
- Pre-existing CD4 T cell help boosts antibody responses but has limited impact on germinal center, antigen-specific B cell frequencies after influenza infection.Frontiers in immunology · 2023Article
- The Autophagy Receptor TAX1BP1 (T6BP) improves antigen presentation by MHC-II molecules.EMBO reports · 2022Article
- Transcriptomic analysis of the innate immune signatures of a SARS-CoV-2 protein subunit vaccine ZF2001 and an mRNA vaccine RRV.Emerging microbes & infections · 2022Article
- Innate immune mechanisms of mRNA vaccines.Immunity · 2022Review
- HIV-1-Infected CD4Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- A single-shot adenoviral vaccine provides hemagglutinin stalk-mediated protection against heterosubtypic influenza challenge in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Lysosomes and lysosome-related organelles in immune responses.FEBS open bio · 2022Review
- Immunopeptidomic analysis of influenza A virus infected human tissues identifies internal proteins as a rich source of HLA ligands.PLoS pathogens · 2022Article
- HIV-1Pathogens (Basel, Switzerland) · 2021Review
- Article
- Type II alveolar cell MHCII improves respiratory viral disease outcomes while exhibiting limited antigen presentation.Nature communications · 2021Article
- Cellular self-cannibalism helps immune cells fight the flu.The FEBS journal · 2021Article
- CD4+ follicular regulatory T cells optimize the influenza virus-specific B cell response.The Journal of experimental medicine · 2021Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with major histocompatibility complex class II molecules. Alternative pathways of epitope production have been identified, but their contributions to host defense have not been established. We show here in a mouse infection model that the CD4+ T cell response to influenza, critical for durable protection from the virus, is driven principally by unconventional processing of antigen synthesized within the infected antigen-presenting cell, not by classical processing of endocytosed virions or material from infected cells. Investigation of the cellular components involved, including the H2-M molecular chaperone, the proteasome and γ-interferon-inducible lysosomal thiol reductase revealed considerable heterogeneity in the generation of individual epitopes, an arrangement that ensures peptide diversity and broad CD4+ T cell engagement. These results could fundamentally revise strategies for rational vaccine design and may lead to key insights into the induction of autoimmune and anti-tumor responses.
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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.