TCR repertoire analysis reveals phosphoantigen-induced polyclonal proliferation of Vγ9Vδ2 T cells in neonates and adults
Standard
TCR repertoire analysis reveals phosphoantigen-induced polyclonal proliferation of Vγ9Vδ2 T cells in neonates and adults. / Fichtner, Alina S; Bubke, Anja; Rampoldi, Francesca; Tan, Likai; Wilharm, Anneke; Steinbrück, Lars; Schultze-Florey, Christian; von Kaisenberg, Constantin; Prinz, Immo; Herrmann, Thomas; Ravens, Sarina.
in: J LEUKOCYTE BIOL, Jahrgang 107, Nr. 6, 06.2020, S. 1023-1032.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - TCR repertoire analysis reveals phosphoantigen-induced polyclonal proliferation of Vγ9Vδ2 T cells in neonates and adults
AU - Fichtner, Alina S
AU - Bubke, Anja
AU - Rampoldi, Francesca
AU - Tan, Likai
AU - Wilharm, Anneke
AU - Steinbrück, Lars
AU - Schultze-Florey, Christian
AU - von Kaisenberg, Constantin
AU - Prinz, Immo
AU - Herrmann, Thomas
AU - Ravens, Sarina
N1 - ©2020 Society for Leukocyte Biology.
PY - 2020/6
Y1 - 2020/6
N2 - The Vγ9Vδ2 T cell subset is the major γδ T cell subset in human peripheral blood and has the unique ability to contribute to immune surveillance by detecting pyrophosphorylated metabolites of isoprenoid synthesis, termed phosphoantigens (pAgs). Vγ9Vδ2 T cells are first detected at midgestation and show postnatal expansion. Interestingly, neonatal Vγ9Vδ2 T cells display a higher TCR repertoire diversity with more public clonotypes and lower pAg responsiveness than in adults. Notably, it is not known whether postnatal changes occur by TCR-dependent reactivity to pAg exposure. Here, we applied next-generation sequencing of γδ TCR repertoires to understand potential differences in the pAg-mediated response of neonatal and adult Vγ9Vδ2 T cells at the level of the expressed γδ TCR. We observed a polyclonal pAg-induced response of neonatal and adult Vγ9Vδ2 T cells, albeit neonatal γδ T cells showed less in vitro pAg responsiveness. Neonatal Vγ9Vδ2 T cells displayed a less pronounced bias for Jδ1 usage and a more frequent use of Jδ2 or Jδ3 that remained stable after pAg exposure. In addition, public and private Vδ2 TRD clones took part in the polyclonal pAg-induced response in neonates and adults. In conclusion, adult and neonatal Vγ9Vδ2 T cells both undergo polyclonal pAg-induced proliferation, whereas especially adult Vγ9Vδ2 T cells display a high stability at the level of the expressed TCR repertoire.
AB - The Vγ9Vδ2 T cell subset is the major γδ T cell subset in human peripheral blood and has the unique ability to contribute to immune surveillance by detecting pyrophosphorylated metabolites of isoprenoid synthesis, termed phosphoantigens (pAgs). Vγ9Vδ2 T cells are first detected at midgestation and show postnatal expansion. Interestingly, neonatal Vγ9Vδ2 T cells display a higher TCR repertoire diversity with more public clonotypes and lower pAg responsiveness than in adults. Notably, it is not known whether postnatal changes occur by TCR-dependent reactivity to pAg exposure. Here, we applied next-generation sequencing of γδ TCR repertoires to understand potential differences in the pAg-mediated response of neonatal and adult Vγ9Vδ2 T cells at the level of the expressed γδ TCR. We observed a polyclonal pAg-induced response of neonatal and adult Vγ9Vδ2 T cells, albeit neonatal γδ T cells showed less in vitro pAg responsiveness. Neonatal Vγ9Vδ2 T cells displayed a less pronounced bias for Jδ1 usage and a more frequent use of Jδ2 or Jδ3 that remained stable after pAg exposure. In addition, public and private Vδ2 TRD clones took part in the polyclonal pAg-induced response in neonates and adults. In conclusion, adult and neonatal Vγ9Vδ2 T cells both undergo polyclonal pAg-induced proliferation, whereas especially adult Vγ9Vδ2 T cells display a high stability at the level of the expressed TCR repertoire.
KW - Adult
KW - Cell Proliferation/drug effects
KW - Clone Cells
KW - Fetal Blood/cytology
KW - Gene Expression
KW - High-Throughput Nucleotide Sequencing
KW - Humans
KW - Infant, Newborn
KW - Interleukin-2/pharmacology
KW - Lymphocyte Activation/drug effects
KW - Organophosphates/pharmacology
KW - Phosphoproteins/genetics
KW - Primary Cell Culture
KW - Receptors, Antigen, T-Cell, gamma-delta/genetics
KW - T-Lymphocyte Subsets/cytology
KW - Zoledronic Acid/pharmacology
U2 - 10.1002/JLB.1MA0120-427RR
DO - 10.1002/JLB.1MA0120-427RR
M3 - SCORING: Journal article
C2 - 32064671
VL - 107
SP - 1023
EP - 1032
JO - J LEUKOCYTE BIOL
JF - J LEUKOCYTE BIOL
SN - 0741-5400
IS - 6
ER -