T细胞受体
表位
主要组织相容性复合体
抗原
细胞生物学
T细胞
生物
CD8型
B细胞受体
B细胞
免疫学
免疫系统
抗体
作者
Alok V. Joglekar,Michael T. Leonard,John D. Jeppson,Margaret Swift,Guideng Li,Stephanie Wong,Songming Peng,Jesse M. Zaretsky,James R. Heath,Antoni Ribas,Michael T. Bethune,David Baltimore
出处
期刊:Nature Methods
[Springer Nature]
日期:2019-01-28
卷期号:16 (2): 191-198
被引量:107
标识
DOI:10.1038/s41592-018-0304-8
摘要
CD8+ T cells recognize and eliminate tumors in an antigen-specific manner. Despite progress in characterizing the antitumor T cell repertoire and function, the identification of target antigens remains a challenge. Here we describe the use of chimeric receptors called signaling and antigen-presenting bifunctional receptors (SABRs) in a cell-based platform for T cell receptor (TCR) antigen discovery. SABRs present an extracellular complex comprising a peptide and major histocompatibility complex (MHC), and induce intracellular signaling via a TCR-like signal after binding with a cognate TCR. We devised a strategy for antigen discovery using SABR libraries to screen thousands of antigenic epitopes. We validated this platform by identifying the targets recognized by public TCRs of known specificities. Moreover, we extended this approach for personalized neoantigen discovery. Engineered, bifunctional receptors present antigens and initiate signaling in response to binding to the cognate T cell receptor. Libraries built with SABRs can screen thousands of epitopes for the discovery of T cell target antigens.
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