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
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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 journal › SCORING: Journal article › Research › peer-review
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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 -