ArticlePLoS pathogens2010
HIV controller CD4+ T cells respond to minimal amounts of Gag antigen due to high TCR avidity.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Trial to evaluate the immunogenicity and safety of a melanoma helper peptide vaccine plus incomplete Freund's adjuvant, cyclophosphamide, and polyICLC (Mel63).Journal for immunotherapy of cancer · 2021Trial
- The elite controller phenotype.Current opinion in HIV and AIDS · 2026Review
- RhCMV expands CCR5+ memory T cells and promotes SIV reservoir seeding in the gut mucosa.JCI insight · 2026Article
- A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design.The Journal of experimental medicine · 2023Article
- Autophagy-dependent glutaminolysis drives superior IL21 production in HIV-1-specific CD4 T cells.Autophagy · 2022Article
- Enhanced Cross-Reactive and Polyfunctional Effector-Memory T Cell Responses by ICVAX-a Human PD1-Based Bivalent HIV-1 Gag-p41 Mosaic DNA Vaccine.Journal of virology · 2022Article
- Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry.Nature communications · 2022Article
- Safety and durability of AGT103-T autologous T cell therapy for HIV infection in a Phase 1 trial.Frontiers in medicine · 2022Article
- A phase 1 study of NY-ESO-1 vaccine + anti-CTLA4 antibody Ipilimumab (IPI) in patients with unresectable or metastatic melanoma.Oncoimmunology · 2021Article
- Role of CD4+ T Cells in the Control of Viral Infections: Recent Advances and Open Questions.International journal of molecular sciences · 2021Review
- HLA class II-Restricted CD8+ T cells in HIV-1 Virus Controllers.Scientific reports · 2019Article
- Article
- Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease.PLoS pathogens · 2018Article
- DNA Vaccination by Electroporation Amplifies Broadly Cross-Restricted Public TCR Clonotypes Shared with HIV Controllers.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Cytomegalovirus (CMV) Epitope-Specific CD4Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- AJournal of immunology (Baltimore, Md. : 1950) · 2017Article
- Expansion and retention of pulmonary CD4Vaccine · 2017Article
- Low Antigen Dose in Adjuvant-Based Vaccination Selectively Induces CD4 T Cells with Enhanced Functional Avidity and Protective Efficacy.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Particular activation phenotype of T cells expressing HLA-DR but not CD38 in GALT from HIV-controllers is associated with immune regulation and delayed progression to AIDS.Immunologic research · 2016Article
- Public T cell receptors confer high-avidity CD4 responses to HIV controllers.The Journal of clinical investigation · 2016Article
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIV controllers are rare individuals who spontaneously control HIV replication in the absence of antiretroviral treatment. Emerging evidence indicates that HIV control is mediated through very active cellular immune responses, though how such responses can persist over time without immune exhaustion is not yet understood. To investigate the nature of memory CD4+ T cells responsible for long-term anti-HIV responses, we characterized the growth kinetics, Vbeta repertoire, and avidity for antigen of patient-derived primary CD4+ T cell lines. Specific cell lines were obtained at a high rate for both HIV controllers (16/17) and efficiently treated patients (19/20) in response to the immunodominant Gag293 peptide. However, lines from controllers showed faster growth kinetics than those of treated patients. After normalizing for growth rates, IFN-gamma responses directed against the immunodominant Gag293 peptide showed higher functional avidity in HIV controllers, indicating differentiation into highly efficient effector cells. In contrast, responses to Gag161, Gag263, or CMV peptides did not differ between groups. Gag293-specific CD4+ T cells were characterized by a diverse Vbeta repertoire, suggesting that multiple clones contributed to the high avidity CD4+ T cell population in controllers. The high functional avidity of the Gag293-specific response could be explained by a high avidity interaction between the TCR and the peptide-MHC complex, as demonstrated by MHC class II tetramer binding. Thus, HIV controllers harbor a pool of memory CD4+ T cells with the intrinsic ability to recognize minimal amounts of Gag antigen, which may explain how they maintain an active antiviral response in the face of very low viremia.
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