ArticleAIDS (London, England)2010
Fine-tuning of T-cell receptor avidity to increase HIV epitope variant recognition by cytotoxic T lymphocytes.
Article in AIDS (London, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- T-cell receptor/CD28-targeted immunotherapeutics selectively drive naive T-cell expansion to generate functional HIV-specific responses.Journal of virology · 2025Article
- Bispecific antibodies cross-link and redirect CD8Science advances · 2025Article
- Therapeutic Vaccines for the Treatment of HIV.Translational research : the journal of laboratory and clinical medicine · 2020Review
- Chimeric Antigen Receptors Targeting Human Cytomegalovirus.The Journal of infectious diseases · 2020Article
- Non-synonymous Substitutions in HIV-1 GAG Are Frequent in Epitopes Outside the Functionally Conserved Regions and Associated With Subtype Differences.Frontiers in microbiology · 2020Article
- Lentiviral Vector-Based Dendritic Cell Vaccine Suppresses HIV Replication in Humanized Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- T cell antigen discovery via signaling and antigen-presenting bifunctional receptors.Nature methods · 2019Article
- Cross-Reactivity against Multiple HIV-1 Epitopes Is Characteristic of HIV-1-Specific Cytotoxic T Lymphocyte Clones.Journal of virology · 2018Article
- HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes.PLoS pathogens · 2017Article
- Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir.The Journal of infectious diseases · 2017Review
- HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies.Journal of virology · 2016Article
- Genetically modified human CD4(+) T cells can be evaluated in vivo without lethal graft-versus-host disease.Immunology · 2016Article
- Clonotypically similar hybrid αβ T cell receptors can exhibit markedly different surface expression, antigen specificity and cross-reactivity.Clinical and experimental immunology · 2015Article
- Generation of β cell-specific human cytotoxic T cells by lentiviral transduction and their survival in immunodeficient human leucocyte antigen-transgenic mice.Clinical and experimental immunology · 2015Article
- TCR affinity associated with functional differences between dominant and subdominant SIV epitope-specific CD8+ T cells in Mamu-A*01+ rhesus monkeys.PLoS pathogens · 2014Article
- Increased sequence coverage through combined targeting of variant and conserved epitopes correlates with control of HIV replication.Journal of virology · 2014Article
- Review
- Innate and Adaptive Immunity in Long-Term Non-Progression in HIV Disease.Frontiers in immunology · 2013Article
- CTL responses of high functional avidity and broad variant cross-reactivity are associated with HIV control.PloS one · 2012Article
- Definition of the viral targets of protective HIV-1-specific T cell responses.Journal of translational medicine · 2011Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveT-cell receptor (TCR) gene therapy is an approach being considered for HIV-1, but epitope mutation is a significant barrier. We assessed whether HIV-specific TCR can be modified to have broader coverage of epitope variants by recombining polymorphisms between public clonotype TCR sequences.
designPublic clonotype TCRs recognizing the same epitope often differ by polymorphisms in their third complementarity determining regions (CDR3). We assessed whether novel combinations of such polymorphisms could improve TCR recognition of epitope variation.
methodsA TCR recognizing the HLA A*0201-restricted epitope SLYNTVATL (Gag 77-85, SL9) was engineered to have combinations of four polymorphisms in the CDR3 regions compared to another SL9-specific TCR. These novel TCRs were screened for functional avidities against SL9 epitope variants and abilities to mediate cytotoxic T-lymphocyte suppression of HIV-1 containing the same epitope variants.
resultsThe TCRs varied modestly in functional avidities for SL9 variants, due to alterations in affinity. This translated to differences in antiviral activities against HIV-1 when functional avidity changes crossed the previously defined threshold required for efficient recognition of HIV-1-infected cells. Higher avidity TCR mutants had generally broader recognition of SL9 variants.
conclusionThese results indicate that rationally targeted increases in functional avidities can be utilized to maximize the antiviral breadth of transgenic TCRs. In contrast to previously reported random mutagenesis to markedly increase functional avidities, tuning through recombining naturally occurring polymorphisms may offer a more physiologic approach that minimizes the risk of deleterious TCR reactivities.
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