Systematic pattern analyses of Vδ2+ TCRs reveal that shared "public" Vδ2+ γδ T cell clones are a consequence of rearrangement bias and a higher expansion status

Standard

Systematic pattern analyses of Vδ2+ TCRs reveal that shared "public" Vδ2+ γδ T cell clones are a consequence of rearrangement bias and a higher expansion status. / Deng, Lihua; Harms, Anna; Ravens, Sarina; Prinz, Immo; Tan, Likai.

In: FRONT IMMUNOL, Vol. 13, 960920, 27.09.2022.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

APA

Vancouver

Bibtex

@article{0c64af1b4d3a421e865b4a857e5bc8c4,
title = "Systematic pattern analyses of Vδ2+ TCRs reveal that shared {"}public{"} Vδ2+ γδ T cell clones are a consequence of rearrangement bias and a higher expansion status",
abstract = "BACKGROUND: Vγ9Vδ2+ T cells are a major innate T cell subset in human peripheral blood. Their Vδ2+ VDJ-rearrangements are short and simple in the fetal thymus and gradually increase in diversity and CDR3 length along with development. So-called {"}public{"} versions of Vδ2+ TCRs are shared among individuals of all ages. However, it is unclear whether such frequently occurring {"}public{"} Vγ9Vδ2+ T cell clones are derived from the fetal thymus and whether they are fitter to proliferate and persist than infrequent {"}private{"} clones.METHODS: Shared {"}public{"} Vδ2+ TCRs were identified from Vδ2+ TCR-repertoires collected from 89 individuals, including newborns (cord blood), infants, and adults (peripheral blood). Distance matrices of Vδ2+ CDR3 were generated by TCRdist3 and then embedded into a UMAP for visualizing the heterogeneity of Vδ2+ TCRs.RESULTS: Vδ2+ CDR3 distance matrix embedded by UMAP revealed that the heterogeneity of Vδ2+ TCRs is primarily determined by the J-usage and CDR3aa length, while age or publicity-specific motifs were not found. The most prevalent public Vδ2+ TCRs showed germline-like rearrangement with low N-insertions. Age-related features were also identified. Public Vδ2+ TRDJ1 TCRs from cord blood showed higher N-insertions and longer CDR3 lengths. Synonymous codons resulting from VDJ rearrangement also contribute to the generation of public Vδ2+ TCRs. Each public TCR was always produced by multiple different transcripts, even with different D gene usage, and the publicity of Vδ2+ TCRs was positively associated with expansion status.CONCLUSION: To conclude, the heterogeneity of Vδ2+ TCRs is mainly determined by TRDJ-usage and the length of CDR3aa sequences. Public Vδ2+ TCRs result from germline-like rearrangement and synonymous codons, associated with a higher expansion status.",
keywords = "Adult, Infant, Infant, Newborn, Humans, Receptors, Antigen, T-Cell, gamma-delta/genetics, T-Lymphocyte Subsets, Intraepithelial Lymphocytes, Clone Cells, Thymus Gland",
author = "Lihua Deng and Anna Harms and Sarina Ravens and Immo Prinz and Likai Tan",
note = "Copyright {\textcopyright} 2022 Deng, Harms, Ravens, Prinz and Tan.",
year = "2022",
month = sep,
day = "27",
doi = "10.3389/fimmu.2022.960920",
language = "English",
volume = "13",
journal = "FRONT IMMUNOL",
issn = "1664-3224",
publisher = "Lausanne : Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Systematic pattern analyses of Vδ2+ TCRs reveal that shared "public" Vδ2+ γδ T cell clones are a consequence of rearrangement bias and a higher expansion status

AU - Deng, Lihua

AU - Harms, Anna

AU - Ravens, Sarina

AU - Prinz, Immo

AU - Tan, Likai

N1 - Copyright © 2022 Deng, Harms, Ravens, Prinz and Tan.

PY - 2022/9/27

Y1 - 2022/9/27

N2 - BACKGROUND: Vγ9Vδ2+ T cells are a major innate T cell subset in human peripheral blood. Their Vδ2+ VDJ-rearrangements are short and simple in the fetal thymus and gradually increase in diversity and CDR3 length along with development. So-called "public" versions of Vδ2+ TCRs are shared among individuals of all ages. However, it is unclear whether such frequently occurring "public" Vγ9Vδ2+ T cell clones are derived from the fetal thymus and whether they are fitter to proliferate and persist than infrequent "private" clones.METHODS: Shared "public" Vδ2+ TCRs were identified from Vδ2+ TCR-repertoires collected from 89 individuals, including newborns (cord blood), infants, and adults (peripheral blood). Distance matrices of Vδ2+ CDR3 were generated by TCRdist3 and then embedded into a UMAP for visualizing the heterogeneity of Vδ2+ TCRs.RESULTS: Vδ2+ CDR3 distance matrix embedded by UMAP revealed that the heterogeneity of Vδ2+ TCRs is primarily determined by the J-usage and CDR3aa length, while age or publicity-specific motifs were not found. The most prevalent public Vδ2+ TCRs showed germline-like rearrangement with low N-insertions. Age-related features were also identified. Public Vδ2+ TRDJ1 TCRs from cord blood showed higher N-insertions and longer CDR3 lengths. Synonymous codons resulting from VDJ rearrangement also contribute to the generation of public Vδ2+ TCRs. Each public TCR was always produced by multiple different transcripts, even with different D gene usage, and the publicity of Vδ2+ TCRs was positively associated with expansion status.CONCLUSION: To conclude, the heterogeneity of Vδ2+ TCRs is mainly determined by TRDJ-usage and the length of CDR3aa sequences. Public Vδ2+ TCRs result from germline-like rearrangement and synonymous codons, associated with a higher expansion status.

AB - BACKGROUND: Vγ9Vδ2+ T cells are a major innate T cell subset in human peripheral blood. Their Vδ2+ VDJ-rearrangements are short and simple in the fetal thymus and gradually increase in diversity and CDR3 length along with development. So-called "public" versions of Vδ2+ TCRs are shared among individuals of all ages. However, it is unclear whether such frequently occurring "public" Vγ9Vδ2+ T cell clones are derived from the fetal thymus and whether they are fitter to proliferate and persist than infrequent "private" clones.METHODS: Shared "public" Vδ2+ TCRs were identified from Vδ2+ TCR-repertoires collected from 89 individuals, including newborns (cord blood), infants, and adults (peripheral blood). Distance matrices of Vδ2+ CDR3 were generated by TCRdist3 and then embedded into a UMAP for visualizing the heterogeneity of Vδ2+ TCRs.RESULTS: Vδ2+ CDR3 distance matrix embedded by UMAP revealed that the heterogeneity of Vδ2+ TCRs is primarily determined by the J-usage and CDR3aa length, while age or publicity-specific motifs were not found. The most prevalent public Vδ2+ TCRs showed germline-like rearrangement with low N-insertions. Age-related features were also identified. Public Vδ2+ TRDJ1 TCRs from cord blood showed higher N-insertions and longer CDR3 lengths. Synonymous codons resulting from VDJ rearrangement also contribute to the generation of public Vδ2+ TCRs. Each public TCR was always produced by multiple different transcripts, even with different D gene usage, and the publicity of Vδ2+ TCRs was positively associated with expansion status.CONCLUSION: To conclude, the heterogeneity of Vδ2+ TCRs is mainly determined by TRDJ-usage and the length of CDR3aa sequences. Public Vδ2+ TCRs result from germline-like rearrangement and synonymous codons, associated with a higher expansion status.

KW - Adult

KW - Infant

KW - Infant, Newborn

KW - Humans

KW - Receptors, Antigen, T-Cell, gamma-delta/genetics

KW - T-Lymphocyte Subsets

KW - Intraepithelial Lymphocytes

KW - Clone Cells

KW - Thymus Gland

U2 - 10.3389/fimmu.2022.960920

DO - 10.3389/fimmu.2022.960920

M3 - SCORING: Journal article

C2 - 36275749

VL - 13

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

M1 - 960920

ER -