Identification of TRDV-TRAJ V domains in human and mouse T-cell receptor repertoires.

T cell receptor (TR) TCR TRDV-TRAJ TRDV1 V-(D)-J rearrangement hybrid V-domain

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2023
Historique:
received: 31 08 2023
accepted: 30 10 2023
medline: 11 12 2023
pubmed: 11 12 2023
entrez: 11 12 2023
Statut: epublish

Résumé

Here, we describe the identification of two T-cell receptors (TRs) containing TRDV genes in their TRA chains, the first one in human and the second one in mouse. First, using 5'RACE on a mixed lymphocyte-tumor cell culture (MLTC), we identified TRDV1 5'-untranslated region (UTR) and complete coding sequence rearranged productively to TRAJ24. Single-cell TR RNA sequencing (RNA-seq) of the MLTC, conducted to identify additional clonotypes, revealed that the analysis software detected the hybrid TRDV-TRAJ TRA (TRA) chain but excluded it from the final results. In a separate project, we performed TR sequencing of tumor-infiltrating lymphocytes (TILs) in a murine tumor model. Here, the predominant clonotype contained a TRA chain with a TRDV2-2-TRAJ49 rearrangement. Again, the hybrid TRA chain was not reported in the final results. Transfection of both TR cDNAs resulted in cell surface localization of TR together with CD3, suggesting a productive protein in both cases. Tumor recognition of the

Identifiants

pubmed: 38077312
doi: 10.3389/fimmu.2023.1286688
pmc: PMC10702483
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1286688

Informations de copyright

Copyright © 2023 Volkmar, Fakhr, Zens, Bury, Offringa, Gordon, Huduti, Wölfel and Wölfel.

Déclaration de conflit d'intérêts

JG is currently employed at BioNtech. While conducting the research contributing to this manuscript, JG was employed at Internal Medicine III. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Michael Volkmar (M)

TCR Discovery Platform, Helmholtz Institute for Translational Oncology (HI-TRON) Mainz, Mainz, Germany.

Elham Fakhr (E)

TCR Discovery Platform, Helmholtz Institute for Translational Oncology (HI-TRON) Mainz, Mainz, Germany.

Stefan Zens (S)

Department D200, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Alice Bury (A)

Helmholtz Institute for Translational Oncology (HI-TRON) Mainz, Mainz, Germany.

Rienk Offringa (R)

Department D200, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Jessica Gordon (J)

BioNtech, Deptartment Immunotherapies & Preclinical Research, Cellular Biomarker and Immunology Research Team, Mainz, Germany.

Enes Huduti (E)

Helmholtz Institute for Translational Oncology (HI-TRON) Mainz, Mainz, Germany.

Thomas Wölfel (T)

Internal Medicine III, University Cancer Center (UCT), Research Center for Immunotherapy (FZI), University Medical Center (UMC) of the Johannes Gutenberg University Mainz and German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Mainz, Germany.

Catherine Wölfel (C)

Internal Medicine III, University Cancer Center (UCT), Research Center for Immunotherapy (FZI), University Medical Center (UMC) of the Johannes Gutenberg University Mainz and German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Mainz, Germany.

Classifications MeSH