A T Cell Receptor Sequencing-Based Assay Identifies Cross-Reactive Recall CD8 + T Cell Clonotypes Against Autologous HIV-1 Epitope Variants.

Autor:	Chan HY; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine, Baltimore, MD, United States.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, United States., Zhang J; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine, Baltimore, MD, United States.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, United States., Garliss CC; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States., Kwaa AK; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States., Blankson JN; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States.; Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine, Baltimore, MD, United States., Smith KN; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine, Baltimore, MD, United States.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 Apr 07; Vol. 11, pp. 591. Date of Electronic Publication: 2020 Apr 07 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.00591
Abstrakt:	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 + 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. (Copyright © 2020 Chan, Zhang, Garliss, Kwaa, Blankson and Smith.)
Databáze:	MEDLINE
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