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A common genetic variation regulates the development of Vγ9Vδ2 versus nonVγ9Vδ2 γδ T cells

par Verdebout, Isoline ;Sánchez Sánchez, Guillem ;Tafesse, Yohannes ;Dauby, Nicolas ;Cogan, Alexandra ;donner, catherine ;Papadopoulou, Maria ;Vermijlen, David
Référence Joint Belgian-Dutch Immunology Meeting 2023 (20-21/11/2023: Flanders Meeting & Convention Center Antwerp, Antwerp, Belgium)
Publication Publié, 2023-09-10

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Résumé :

A common genetic variation regulates the development of Vγ9Vδ2 versus nonVγ9Vδ2 γδ T cells3ULB Center for Research in Immunology, Université libre de Bruxelles (ULB), Brussels, Belgium4 WEL Research Institute, WELBIO department, , Wavre, Belgium7 Department of Obstetrics and Gynecology, Hôpital Erasme, Université libre de Bruxelles (ULB), Brussels, BelgiumIn humans, үδ T cells can be subdivided into innate-like Vү9Vδ2 T cells and adaptive-like nonVү9Vδ2 үδ T cells, dictated by the differential usage of variable (V)ү and Vδ chains in their T cell receptor (TCR). The prevalence of these subsets and thus the Vү and Vδ usage can be highly variable between individuals, including in antigen-inexperienced cord blood. It is not clear whether genetic factors exist that can drive this variable prevalence.Here we identified a common genetic variation driving differential prevalence of үδ T cell subsets, using multi-parameter flow cytometry and TCR/complementarity-determining region 3 (CDR3) repertoire analysis by high-throughput sequencing. This genetic variation influenced the frequencies of Vү9Vδ2 versus nonVү9Vδ2 T cells in antigen-unexperienced term-delivery cord blood. Furthermore, these differences were already present at earlier gestation times (20 weeks) of the fetus. In addition, among the nonVү9Vδ2 T cells, differential usage of the variable gene segment of the ү locus (TRGV) could be observed. We are currently verifying the influence of this genetic variation on the үδ thymocyte development by investigating human thymuses ex-vivo and in artificial thymic organ cultures.Overall, we identified a SNP that appears to regulate the development of Vγγ9Vδδ2 and nonVγγ9Vδδ2 T cells by influencing the TRGV and TRDV usage..