Open AccessAdaptive Nanoparticle Platforms for High Throughput Expansion and Detection of Antigen-Specific T cells
Author(s) -
John W. Hickey,
Ariel Isser,
Sebastian F. Salathe,
Kayla M. Gee,
Meng Hsuan Hsiao,
Wasamah Shaikh,
Nkechi C. Uzoukwu,
Joan Glick Bieler,
HaiQuan Mao,
Jonathan P. Schneck
Publication year - 2020
Publication title -
nano letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.853
H-Index - 488
eISSN - 1530-6992
pISSN - 1530-6984
DOI - 10.1021/acs.nanolett.0c01511
Subject(s) - antigen , immune system , acquired immune system , epitope , cytotoxic t cell , microbiology and biotechnology , t cell , biology , chemistry , immunology , in vitro , biochemistry
T cells are critical players in disease; yet, their antigen-specificity has been difficult to identify, as current techniques are limited in terms of sensitivity, throughput, or ease of use. To address these challenges, we increased the throughput and translatability of magnetic nanoparticle-based artificial antigen presenting cells (aAPCs) to enrich and expand (E+E) murine or human antigen-specific T cells. We streamlined enrichment, expansion, and aAPC production processes by enriching CD8+ T cells directly from unpurified immune cells, increasing parallel processing capacity of aAPCs in a 96-well plate format, and designing an adaptive aAPC that enables multiplexed aAPC construction for E+E and detection. We applied these adaptive platforms to process and detect CD8+ T cells specific for rare cancer neoantigens, commensal bacterial cross-reactive epitopes, and human viral and melanoma antigens. These innovations dramatically increase the multiplexing ability and decrease the barrier to adopt for investigating antigen-specific T cell responses.