TCR repertoire analysis reveals phosphoantigen‐induced polyclonal proliferation of Vγ9Vδ2 T cells in neonates and adults

The Vgamma9Vdelta2 T cell subset is the major gammadelta 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). Vgamma9Vdelta2 T cells are first detected at midgestation and show postnatal expansion. Interestingly, neonatal Vgamma9Vdelta2 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 gammadelta TCR repertoires to understand potential differences in the pAg-mediated response of neonatal and adult Vgamma9Vdelta2 T cells at the level of the expressed gammadelta TCR. We observed a polyclonal pAg-induced response of neonatal and adult Vgamma9Vdelta2 T cells, albeit neonatal gammadelta T cells showed less in vitro pAg responsiveness. Neonatal Vgamma9Vdelta2 T cells displayed a less pronounced bias for Jdelta1 usage and a more frequent use of Jdelta2 or Jdelta3 that remained stable after pAg exposure. In addition, public and private Vdelta2 TRD clones took part in the polyclonal pAg-induced response in neonates and adults. In conclusion, adult and neonatal Vgamma9Vdelta2 T cells both undergo polyclonal pAg-induced proliferation, whereas especially adult Vgamma9Vdelta2 T cells display a high stability at the level of the expressed TCR repertoire.