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A T Cell Receptor Sequencing-Based Assay Identifies Cross-Reactive Recall CD8+ T Cell Clonotypes Against Autologous HIV-1 Epitope Variants.
- Source :
- Frontiers in Immunology; 4/7/2020, p1-9, 9p
- Publication Year :
- 2020
-
Abstract
- HIV-1 positive elite controllers or suppressors control viral replication without antiretroviral therapy, likely via CTL-mediated elimination of infected cells, and therefore represent a model of an HIV-1 functional cure. Efforts to cure HIV-1 accordingly rely on the existence or generation of antigen-specific cytotoxic T lymphocytes (CTL) to eradicate infected cells upon reversal of latency. Detecting and quantifying these HIV-1-specific CTL responses will be crucial for developing vaccine and T cell-based immunotherapies. A recently developed assay, called MANAFEST, uses T cell receptor (TCR) Vβ sequencing of peptide-stimulated cultures followed by a bioinformatic pipeline to identify neoantigen-specific T cells in cancer patients. This assay is more sensitive than conventional immune assays and therefore has the possibility to identify HIV-1 antigenic targets that have not been previously explored for vaccine or T cell immunotherapeutic strategies. Here we show that a modified version of the MANAFEST assay, called ViraFEST, can identify memory CD8<superscript>+</superscript> T cell responses against autologous HIV-1 Gag and Nef epitope variants in an elite suppressor. Nine TCR Vβ clonotypes were identified and 6 of these were cross-reactive for autologous variants or known escape variants. Our findings are a proof of principle that the ViraFEST assay can be used to detect and monitor these responses for downstream use in immunotherapeutic treatment approaches. [ABSTRACT FROM AUTHOR]
- Subjects :
- T cell receptors
T cells
CYTOTOXIC T cells
CANCER cells
VIRAL replication
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Database :
- Complementary Index
- Journal :
- Frontiers in Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 142633467
- Full Text :
- https://doi.org/10.3389/fimmu.2020.00591