Engineered cell entry links receptor biology with single-cell genomics.
Cell
; 185(26): 4904-4920.e22, 2022 12 22.
Article
en En
| MEDLINE
| ID: mdl-36516854
ABSTRACT
Cells communicate with each other via receptor-ligand interactions. Here, we describe lentiviral-mediated cell entry by engineered receptor-ligand interaction (ENTER) to display ligand proteins, deliver payloads, and record receptor specificity. We optimize ENTER to decode interactions between T cell receptor (TCR)-MHC peptides, antibody-antigen, and other receptor-ligand pairs. A viral presentation strategy allows ENTER to capture interactions between B cell receptor and any antigen. We engineer ENTER to deliver genetic payloads to antigen-specific T or B cells to selectively modulate cellular behavior in mixed populations. Single-cell readout of ENTER by RNA sequencing (ENTER-seq) enables multiplexed enumeration of antigen specificities, TCR clonality, cell type, and states of individual T cells. ENTER-seq of CMV-seropositive patient blood samples reveals the viral epitopes that drive effector memory T cell differentiation and inter-clonal vs. intra-clonal phenotypic diversity targeting the same epitope. ENTER technology enables systematic discovery of receptor specificity, linkage to cell fates, and antigen-specific cargo delivery.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Antígenos de Linfocitos T
/
Internalización del Virus
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article