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ATLAS-seq: a novel microfluidic single-cell TCR screen for highly reactive antigen-specific TCRs

ABSTRACT: Clonotype selection of T cell receptors (TCRs) have been the core component of TCR therapy development. However, the conventional and widely used major histocompatibility complex (MHC) multimer staining technologies focus on high-affinity interactions between TCR and MHC-antigen complex, which may fail to identify TCRs with high efficacy for activating T cells. Here, we developed the Aptamer-based T Lymphocyte Activity Screening and sequencing (ATLAS-seq) method on a microfluidic platform. ATLAS-seq isolates and characterizes activated T cells using an aptamer-based fluorescent molecular sensor to monitor cytokine secretion from single-T cells upon antigen stimulation, followed by single-cell sequencing. As a proof of principle study, we used ATLAS-seq to screen cytomegalovirus (CMV)-reactive TCRs and identified a distinct clonotype population with a higher T cell activation level compared to one recovered by Dextramer staining method. Furthermore, we observed that ATLAS-seq selected TCR clonotypes are more efficient in target cell killing than those from Dextramer staining. Therefore, our ATLAS-seq can provide an efficient workflow to screen highly reactive antigen-specific TCR clonotypes for cancer immunotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234359 | GEO | 2024/10/11

REPOSITORIES: GEO

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