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@article{2376937,
author = {Smirnova, Anastasia O and Miroshnichenkova, Anna M and Belyaeva, Laima D and Kelmanson, Ilya V and Lebedev, Yuri B and Mamedov, Ilgar Z and Chudakov, Dmitriy and Komkov, Alexander Y},
article_location = {LAUSANNE},
article_number = {Sep},
doi = {http://dx.doi.org/10.3389/fimmu.2023.1245175},
keywords = {TRB repertoire; VDJ recombination; NGS - next generation sequencing; T cell; Thymus},
language = {eng},
issn = {1664-3224},
journal = {Frontiers in immunology},
title = {Novel bimodal TRBD1-TRBD2 rearrangements with dual or absent D-region contribute to TRB V-(D)-J combinatorial diversity},
url = {https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1245175/full},
volume = {14},
year = {2023}
}
TY - JOUR
ID - 2376937
AU - Smirnova, Anastasia O - Miroshnichenkova, Anna M - Belyaeva, Laima D - Kelmanson, Ilya V - Lebedev, Yuri B - Mamedov, Ilgar Z - Chudakov, Dmitriy - Komkov, Alexander Y
PY - 2023
TI - Novel bimodal TRBD1-TRBD2 rearrangements with dual or absent D-region contribute to TRB V-(D)-J combinatorial diversity
JF - Frontiers in immunology
VL - 14
IS - Sep
SP - 1-10
EP - 1-10
PB - Frontiers Media S.A.
SN - 16643224
KW - TRB repertoire
KW - VDJ recombination
KW - NGS - next generation sequencing
KW - T cell
KW - Thymus
UR - https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1245175/full
N2 - T-cell receptor (TR) diversity of the variable domains is generated by recombination of both the alpha (TRA) and beta (TRB) chains. The textbook process of TRB chain production starts with TRBD and TRBJ gene rearrangement, followed by the rearrangement of a TRBV gene to the partially rearranged D-J gene. Unsuccessful V-D-J TRB rearrangements lead to apoptosis of the cell. Here, we performed deep sequencing of the poorly explored pool of partial TRBD1-TRBD2 rearrangements in T-cell genomic DNA. We reconstructed full repertoires of human partial TRBD1-TRBD2 rearrangements using novel sequencing and validated them by detecting V-D-J recombination-specific byproducts: excision circles containing the recombination signal (RS) joint 5'D2-RS - 3'D1-RS. Identified rearrangements were in compliance with the classical 12/23 rule, common for humans, rats, and mice and contained typical V-D-J recombination footprints. Interestingly, we detected a bimodal distribution of D-D junctions indicating two active recombination sites producing long and short D-D rearrangements. Long TRB D-D rearrangements with two D-regions are coding joints D1-D2 remaining classically on the chromosome. The short TRB D-D rearrangements with no D-region are signal joints, the coding joint D1-D2 being excised from the chromosome. They both contribute to the TRB V-(D)-J combinatorial diversity. Indeed, short D-D rearrangements may be followed by direct V-J2 recombination. Long D-D rearrangements may recombine further with J2 and V genes forming partial D1-D2-J2 and then complete V-D1-D2-J2 rearrangement. Productive TRB V-D1-D2-J2 chains are present and expressed in thousands of clones of human antigen-experienced memory T cells proving their capacity for antigen recognition and actual participation in the immune response.
ER -
SMIRNOVA, Anastasia O, Anna M MIROSHNICHENKOVA, Laima D BELYAEVA, Ilya V KELMANSON, Yuri B LEBEDEV, Ilgar Z MAMEDOV, Dmitriy CHUDAKOV and Alexander Y KOMKOV. Novel bimodal TRBD1-TRBD2 rearrangements with dual or absent D-region contribute to TRB V-(D)-J combinatorial diversity. \textit{Frontiers in immunology}. LAUSANNE: Frontiers Media S.A., 2023, vol.~14, Sep, p.~1-10. ISSN~1664-3224. Available from: https://dx.doi.org/10.3389/fimmu.2023.1245175.
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