生物
T细胞受体
表位
嵌合抗原受体
抗原
受体
主要组织相容性复合体
细胞生物学
抗原呈递
T细胞
计算生物学
B细胞受体
B细胞
遗传学
抗体
免疫系统
作者
Bingfei Yu,Quanming Shi,Julia A. Belk,Kathryn E. Yost,Kevin R. Parker,Rui Li,Betty B. Liu,Huang Huang,Daniel Lingwood,William J. Greenleaf,Mark M. Davis,Ansuman T. Satpathy,Howard Y. Chang
出处
期刊:Cell
[Elsevier]
日期:2022-12-01
卷期号:185 (26): 4904-4920.e22
被引量:14
标识
DOI:10.1016/j.cell.2022.11.016
摘要
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.
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