ArticlePloS one2012
High avidity cytotoxic T lymphocytes can be selected into the memory pool but they are exquisitely sensitive to functional impairment.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- TRP-2 / gp100 DNA vaccine and PD-1 checkpoint blockade combination for the treatment of intracranial tumors.Cancer immunology, immunotherapy : CII · 2024Article
- CD3 downregulation identifies high-avidity, multipotent SARS-CoV-2 vaccine- and recall antigen-specific Th cells with distinct metabolism.JCI insight · 2024Article
- Vaccination with post-translational modified, homocitrullinated peptides induces CD8 T-cell responses that mediate antitumor immunity.Journal for immunotherapy of cancer · 2023Article
- Systematic Determination of TCR-Antigen and Peptide-MHC Binding Kinetics among Field Variants of aJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Cancer Vaccines, Adjuvants, and Delivery Systems.Frontiers in immunology · 2021Review
- A Novel HAGE/WT1-ImmunoBodyFrontiers in oncology · 2021Article
- Novel tumour antigens and the development of optimal vaccine design.Therapeutic advances in vaccines and immunotherapy · 2018Review
- Immunotherapy of WAP-TOncotarget · 2017Article
- Heterogeneity assessment of functional T cell avidity.Scientific reports · 2017Article
- SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors.Oncotarget · 2016Article
- SCIB2, an antibody DNA vaccine encoding NY-ESO-1 epitopes, induces potent antitumor immunity which is further enhanced by checkpoint blockade.Oncoimmunology · 2016Article
- CD4+ T Cell Help Selectively Enhances High-Avidity Tumor Antigen-Specific CD8+ T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Identification of human leukemia antigen A*0201-restricted epitopes derived from epidermal growth factor pathway substrate number 8.Molecular medicine reports · 2015Article
- Identifying Individual T Cell Receptors of Optimal Avidity for Tumor Antigens.Frontiers in immunology · 2015Review
- T cell avidity and tumor immunity: problems and solutions.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2014Article
- Elimination of IL-10-inducing T-helper epitopes from an IGFBP-2 vaccine ensures potent antitumor activity.Cancer research · 2014Article
- HER-2/neu vaccine-primed autologous T-cell infusions for the treatment of advanced stage HER-2/neu expressing cancers.Cancer immunology, immunotherapy : CII · 2014Article
- TCR-Engineered T Cells Meet New Challenges to Treat Solid Tumors: Choice of Antigen, T Cell Fitness, and Sensitization of Tumor Milieu.Frontiers in immunology · 2013Review
- CD8OncoimmunologyArticle
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High avidity cytotoxic T lymphocytes (CTL) are important in viral clearance and anti-tumor immunity, however, mechanisms for their optimal generation and maintenance in vivo remain unclear. Immunizing mice with an antibody-DNA vaccine encoding a single CTL epitope, induces a 100 fold higher avidity response than peptide vaccination with the identical epitope. The high avidity response is retained into memory and can be efficiently reactivated with an antibody-DNA boost. In contrast, reactivation of high avidity CTL with peptide, stimulated responses with a significant drop in avidity, suggesting loss or conversion of the high avidity CTL to lower avidity. Similarly, high avidity T cells maintained ex vivo were exquisitely sensitive to signaling with low doses of peptide (1 ng/ml) giving optimal TCR stimulation and resulting in retained avidity, proliferation and ability to kill specific targets. In contrast, high avidity T cells maintained ex vivo with supraoptimal TCR stimulation (10 µg/ml peptide) resulted in reduced avidity and failure to kill tumor cells. They also failed to proliferate, showed a significant increase in apoptosis and expressed high levels of the exhaustion marker programmed death-1 (PD-1) and low levels of the lymphocyte-activation gene 3 (LAG-3). This suggests high avidity T cells are recruited to the memory pool but can be lost by supraoptimal stimulation in vitro and in vivo. This is characterized by loss of function and an increase in cell death. The remaining CTL, exhibit low functional avidity that is reflected in reduced anti-tumor activity. This could contribute to failure of the immune system to control the growth of tumors and has implications for vaccination strategies and adoptive transfer of T cells.
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