Details

Autor(en) / Beteiligte

• Fahad, Ahmed S
• Chung, Cheng Yu
• López Acevedo, Sheila N
• Boyle, Nicoleen
• Madan, Bharat
• Gutiérrez-González, Matías F
• Matus-Nicodemos, Rodrigo
• Laflin, Amy D
• Ladi, Rukmini R
• Zhou, John
• Wolfe, Jacy
• Llewellyn-Lacey, Sian
• Koup, Richard A
• Douek, Daniel C
• Balfour, Jr, Henry H
• Price, David A
• DeKosky, Brandon J

Titel

Cell activation-based screening of natively paired human T cell receptor repertoires

Ist Teil von

• Scientific reports, 2023-05, Vol.13 (1), p.8011-8011, Article 8011

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Adoptive immune therapies based on the transfer of antigen-specific T cells have been used successfully to treat various cancers and viral infections, but improved techniques are needed to identify optimally protective human T cell receptors (TCRs). Here we present a high-throughput approach to the identification of natively paired human TCRα and TCRβ (TCRα:β) genes encoding heterodimeric TCRs that recognize specific peptide antigens bound to major histocompatibility complex molecules (pMHCs). We first captured and cloned TCRα:β genes from individual cells, ensuring fidelity using a suppression PCR. We then screened TCRα:β libraries expressed in an immortalized cell line using peptide-pulsed antigen-presenting cells and sequenced activated clones to identify the cognate TCRs. Our results validated an experimental pipeline that allows large-scale repertoire datasets to be annotated with functional specificity information, facilitating the discovery of therapeutically relevant TCRs.