Home > Publications database > Identification of TRDV-TRAJ V domains in human and mouse T-cell receptor repertoires. > print |
001 | 286105 | ||
005 | 20240724161214.0 | ||
024 | 7 | _ | |a 10.3389/fimmu.2023.1286688 |2 doi |
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041 | _ | _ | |a English |
082 | _ | _ | |a 610 |
100 | 1 | _ | |a Volkmar, Michael |b 0 |
245 | _ | _ | |a Identification of TRDV-TRAJ V domains in human and mouse T-cell receptor repertoires. |
260 | _ | _ | |a Lausanne |c 2023 |b Frontiers Media |
336 | 7 | _ | |a article |2 DRIVER |
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336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1721830315_9952 |2 PUB:(DE-HGF) |
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520 | _ | _ | |a 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. |
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650 | _ | 7 | |a T cell receptor (TR) |2 Other |
650 | _ | 7 | |a TCR |2 Other |
650 | _ | 7 | |a TRDV-TRAJ |2 Other |
650 | _ | 7 | |a TRDV1 |2 Other |
650 | _ | 7 | |a V-(D)-J rearrangement |2 Other |
650 | _ | 7 | |a hybrid V-domain |2 Other |
700 | 1 | _ | |a Fakhr, Elham |b 1 |
700 | 1 | _ | |a Zens, Stefan |0 P:(DE-He78)17b0a821061db042fe4b6eff379d1ba6 |b 2 |u dkfz |
700 | 1 | _ | |a Bury, Alice |b 3 |
700 | 1 | _ | |a Offringa, Rienk |0 P:(DE-He78)81ae96953d6149e4307057d71a190019 |b 4 |u dkfz |
700 | 1 | _ | |a Gordon, Jessica |b 5 |
700 | 1 | _ | |a Huduti, Enes |b 6 |
700 | 1 | _ | |a Wölfel, Thomas |0 P:(DE-HGF)0 |b 7 |
700 | 1 | _ | |a Wölfel, Catherine |0 P:(DE-He78)9cdc7d76865e19ae92ef6d41f558ed16 |b 8 |u dkfz |
773 | _ | _ | |a 10.3389/fimmu.2023.1286688 |g Vol. 14, p. 1286688 |0 PERI:(DE-600)2606827-8 |p 1286688 |t Frontiers in immunology |v 14 |y 2023 |x 1664-3224 |
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