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In vitro, CD4+ T cells from all donors respond to nickel but the involved \u03b1\u03b2 T\u00a0cell receptor (TCR) repertoire has not been comprehensively analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We introduce CD154 (CD40L) upregulation as a fast, unbiased, and quantitative method to detect nickel\u2010specific CD4+ T cells ex vivo in blood of clinically characterized allergic and non allergic donors. Na\u00efve (CCR7+ CD45RA+) and memory (not na\u00efve) CD154+ CD4+ T\u00a0cells were analyzed by flow cytometry after 5\u00a0hours of stimulation with 200\u00a0\u00b5mol\/L NiSO<jats:sub>4<\/jats:sub>., TCR \u03b1\u2010 and \u03b2\u2010chains of sorted nickel\u2010specific and control cells were studied by high\u2010throughput sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Stimulation of PBMCs with NiSO<jats:sub>4<\/jats:sub>induced CD154 expression on ~0.1% (mean) of na\u00efve and memory CD4+ T cells. In allergic donors with recent positive patch test, memory frequencies further increased ~13\u2010fold and were associated with markers of in vivo activation. CD154 expression was TCR\u2010mediated since single clones could be specifically restimulated. Among nickel\u2010specific CD4+ T cells of allergic and non allergic donors, TCRs expressing the \u03b1\u2010chain segment TRAV9\u20102 or a histidine in their \u03b1\u2010 or \u03b2\u2010chain complementarity determining region 3 (CDR3) were highly overrepresented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Induced CD154 expression represents a reliable method to study nickel\u2010specific 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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.14322","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T20:04:06Z","timestamp":1587067446000},"page":"2574-2586","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["TCRs with segment TRAV9\u20102 or a CDR3 histidine are overrepresented among nickel\u2010specific CD4+ T cells"],"prefix":"10.1111","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5483-1366","authenticated-orcid":false,"given":"Marina","family":"Aparicio\u2010Soto","sequence":"first","affiliation":[{"name":"Department of Chemical and Product Safety German Federal Institute for Risk Assessment Berlin 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