Isolation of Structurally Heterogeneous TCR-CD3 Extracellular Vesicle Subpopulations Using Caliper Strategy

Wen Yin; Haitian Chen; Jianye Cai; Xing Huang; Lang Zhang; Yuzhi Xu; Jun Zheng; Si-Yang Liu; Xiaoyong Zou; Zong Dai; Yang Yang

doi:10.1002/anie.202300954

Isolation of Structurally Heterogeneous TCR-CD3 Extracellular Vesicle Subpopulations Using Caliper Strategy

Angew Chem Int Ed Engl. 2023 Apr 24;62(18):e202300954. doi: 10.1002/anie.202300954. Epub 2023 Mar 27.

Authors

Wen Yin^{1

2

3}, Haitian Chen⁴, Jianye Cai⁴, Xing Huang^{1

2}, Lang Zhang³, Yuzhi Xu³, Jun Zheng⁴, Si-Yang Liu^{1

2}, Xiaoyong Zou³, Zong Dai^{1

2}, Yang Yang⁴

Affiliations

¹ School of Biomedical Engineering, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, 518107, China.
² Guangdong Provincial Key Laboratory of Sensing Technology and Biomedical Instrument, School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen, 518107, China.
³ School of Chemistry, Sun Yat-Sen University, Guangzhou, Guangdong, 510006, China.
⁴ Department of Hepatic Surgery and Liver Transplantation Center, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.

PMID: 36878876
DOI: 10.1002/anie.202300954

Abstract

Cells in different states can release diverse types of extracellular vesicles (EVs) that participate in intracellular communication or pathological processes. The identification and isolation of EV subpopulations are significant to explore their physiological functions and clinical value. In this study, structurally heterogeneous T-cell receptor (TCR)-CD3 EVs were proposed and verified for the first time using a caliper strategy. Two CD3-targeting aptamers were designed in the shape of a caliper with an optimized probe distance and were assembled on gold nanoparticles (Au-Caliper) to distinguish TCR-CD3 monomeric and dimeric EVs (m/dCD3 EVs) in skin-transplanted mouse plasma. Phenotyping and sequencing analysis revealed clear heterogeneity in the isolated m/dCD3 EVs, providing the potential for mCD3 EVs as a candidate biomarker of acute cellular rejection (ACR) and holding great prospects for distinguishing EV subpopulations based on protein oligomerization states.

Keywords: Acute Cellular Rejection; Extracellular Vesicle; Heterogeneity; Subpopulation Isolation; TCR-CD3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers / metabolism
Extracellular Vesicles* / metabolism
Gold / metabolism
Metal Nanoparticles*
Mice
Receptors, Antigen, T-Cell / metabolism

Substances

Gold
Biomarkers
Receptors, Antigen, T-Cell