T细胞受体
Jurkat细胞
生物
T细胞
抗原
贪婪
计算生物学
细胞生物学
免疫学
分子生物学
免疫系统
作者
Matthew Spindler,Ayla L. Nelson,Ellen K Wagner,Natasha Oppermans,John S. Bridgeman,James Heather,Adam S. Adler,Michael A. Asensio,Robert C. Edgar,Yoong Wearn Lim,Everett Meyer,Robert E. Hawkins,Mark Cobbold,D. S. Johnson
标识
DOI:10.1038/s41587-020-0438-y
摘要
T cells engineered to express antigen-specific T cell receptors (TCRs) are potent therapies for viral infections and cancer. However, efficient identification of clinical candidate TCRs is complicated by the size and complexity of T cell repertoires and the challenges of working with primary T cells. Here we present a high-throughput method to identify TCRs with high functional avidity from diverse human T cell repertoires. The approach used massively parallel microfluidics to generate libraries of natively paired, full-length TCRαβ clones, from millions of primary T cells, which were then expressed in Jurkat cells. The TCRαβ-Jurkat libraries enabled repeated screening and panning for antigen-reactive TCRs using peptide major histocompatibility complex binding and cellular activation. We captured more than 2.9 million natively paired TCRαβ clonotypes from six healthy human donors and identified rare (<0.001% frequency) viral-antigen-reactive TCRs. We also mined a tumor-infiltrating lymphocyte sample from a patient with melanoma and identified several tumor-specific TCRs, which, after expression in primary T cells, led to tumor cell killing.
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