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@ARTICLE{Volkmar:286105,
author = {M. Volkmar and E. Fakhr and S. Zens$^*$ and A. Bury and R.
Offringa$^*$ and J. Gordon and E. Huduti and T. Wölfel$^*$
and C. Wölfel$^*$},
title = {{I}dentification of {TRDV}-{TRAJ} {V} domains in human and
mouse {T}-cell receptor repertoires.},
journal = {Frontiers in immunology},
volume = {14},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2023-02681},
pages = {1286688},
year = {2023},
note = {HI-TRON},
abstract = {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 Homo sapiens (Homsap)
TRDV1-containing TR could be demonstrated by IFN Gamma ELISA
ELISpot kit, whereas the Mus musculus (Musmus) TR did not
recognize a tumor-derived cell line. To determine whether
the TRDV-containing TRA chains we detected were rare events
or whether TRDV genes are commonly incorporated into TRA
chains, we queried the NCBI Sequence Read Archive for TR
single-cell RNA-seq data and analyzed 21 human and 23 murine
datasets. We found that especially Homsap TRDV1, Musmus
TRDV1, and to some extent Musmus TRDV2-2 are more commonly
incorporated into TRA chains than several TRAV genes, making
those TRDV genes a relevant contribution to TRA diversity.
TRDV-containing TRA chains are currently excluded from the
final results of V-(D)-J dataset analyses with the
CellRanger software. We provide a work-around to avoid
exclusion of those hybrid TRA chains from the final analysis
results.},
keywords = {T cell receptor (TR) (Other) / TCR (Other) / TRDV-TRAJ
(Other) / TRDV1 (Other) / V-(D)-J rearrangement (Other) /
hybrid V-domain (Other)},
cin = {D200 / FM01},
ddc = {610},
cid = {I:(DE-He78)D200-20160331 / I:(DE-He78)FM01-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38077312},
pmc = {pmc:PMC10702483},
doi = {10.3389/fimmu.2023.1286688},
url = {https://inrepo02.dkfz.de/record/286105},
}