TCRs with segment TRAV9-2 or a CDR3 histidine are overrepresented among nickel-specific CD4+T cells

Aparicio-Soto, Marina; Riedel, Franziska; Leddermann, Melanie; Bacher, Petra; Scheffold, Alexander; Kuhl, Heiner; Timmermann, Bernd; Chudakov, Dmitriy M.; Molin, Sonja; Worm, Margitta; Heine, Guido; Thierse, Hermann-Josef; Luch, Andreas und Siewert, Katherina (2020): TCRs with segment TRAV9-2 or a CDR3 histidine are overrepresented among nickel-specific CD4+T cells. In: Allergy, Bd. 75, Nr. 10: S. 2574-2586

Abstract

Background: Nickel is the most frequent cause of T cell-mediated allergic contact dermatitis worldwide. In vitro, CD4+ T cells from all donors respond to nickel but the involved alpha beta T cell receptor (TCR) repertoire has not been comprehensively analyzed. Methods We introduce CD154 (CD40L) upregulation as a fast, unbiased, and quantitative method to detect nickel-specific CD4+ T cells ex vivo in blood of clinically characterized allergic and non allergic donors. Naive (CCR7+ CD45RA+) and memory (not naive) CD154+ CD4+ T cells were analyzed by flow cytometry after 5 hours of stimulation with 200 mu mol/L NiSO4., TCR alpha- and beta-chains of sorted nickel-specific and control cells were studied by high-throughput sequencing. Results Stimulation of PBMCs with NiSO4 induced CD154 expression on similar to 0.1% (mean) of naive and memory CD4+ T cells. In allergic donors with recent positive patch test, memory frequencies further increased similar to 13-fold and were associated with markers of in vivo activation. CD154 expression was TCR-mediated since single clones could be specifically restimulated. Among nickel-specific CD4+ T cells of allergic and non allergic donors, TCRs expressing the alpha-chain segment TRAV9-2 or a histidine in their alpha- or beta-chain complementarity determining region 3 (CDR3) were highly overrepresented. Conclusions: Induced CD154 expression represents a reliable method to study nickel-specific CD4+ T cells. TCRs with particular features respond in all donors, while strongly increased blood frequencies indicate nickel allergy for some donors. Our approach may be extended to other contact allergens for the further development of diagnostic and predictive in vitro tests.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0105-4538
• Sprache: Englisch