Details

Autor(en) / Beteiligte

• Riedel, Franziska
• Aparicio‐Soto, Marina
• Curato, Caterina
• Münch, Lucas
• Abbas, Amro
• Thierse, Hermann‐Josef
• Peitsch, Wiebke K.
• Luch, Andreas
• Siewert, Katherina

Titel

Unique and common TCR repertoire features of Ni2+‐, Co2+‐, and Pd2+‐specific human CD154 + CD4+ T cells

Ist Teil von

• Allergy (Copenhagen), 2023-01, Vol.78 (1), p.270-282

Ort / Verlag

Zurich: Blackwell Publishing Ltd

Erscheinungsjahr

2023

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Background Apart from Ni2+, Co2+, and Pd2+ ions commonly trigger T cell‐mediated allergic contact dermatitis. However, in vitro frequencies of metal‐specific T cells and the mechanisms of antigen recognition remain unclear. Methods Here, we utilized a CD154 upregulation assay to quantify Ni2+‐, Co2+‐, and Pd2+‐specific CD4+ T cells in peripheral blood mononuclear cells (PBMC). Involved αβ T cell receptor (TCR) repertoires were analyzed by high‐throughput sequencing. Results Peripheral blood mononuclear cells incubation with NiSO4, CoCl2, and PdCl2 increased frequencies of CD154 + CD4+ memory T cells that peaked at ~400 μM. Activation was TCR‐mediated as shown by the metal‐specific restimulation of T cell clones. Most abundant were Pd2+‐specific T cells (mean 3.5%, n = 19), followed by Co2+‐ and Ni2+‐specific cells (0.6%, n = 18 and 0.3%, n = 20) in both allergic and non‐allergic individuals. A strong overrepresentation of the gene segment TRAV9‐2 was unique for Ni2+‐specific TCR (28% of TCR) while Co2+ and Pd2+‐specific TCR favorably expressed TRAV2 (8%) and the TRBV4 gene segment family (21%), respectively. As a second, independent mechanism of metal ion recognition, all analyzed metal‐specific TCR showed a common overrepresentation of a histidine in the complementarity determining region 3 (CDR3; 15% of α‐chains, 34% of β‐chains). The positions of the CDR3 histidine among metal‐specific TCR mirrored those in random repertoires and were conserved among cross‐reactive clonotypes. Conclusions Induced CD154 expression allows a fast and comprehensive detection of Ni2+‐, Co2+‐, and Pd2+‐specific CD4+ T cells. Distinct TCR repertoire features underlie the frequent activation and cross‐reactivity of human metal‐specific T cells. Ni2+‐, Co2+‐, and Pd2+‐specific CD4+ T cells can be detected by a short‐term CD154 upregulation assay. Overrepresentation of certain individual gene segments or a CDR3 histidine represent distinct TCR repertoire characteristics that underlie metal ion binding and cross‐reactivity. Frequent metal‐specific T cell activation in allergic and non‐allergic individuals challenges blood‐based allergy detection in vitro.Abbreviation: APC, antigen‐presenting cells; CDR3, complementarity determining region 3; Co, cobalt; HTS, high‐throughput sequencing; MHC, major histocompatibility complex; Ni, nickel; PBMC, peripheral blood mononuclear cells; Pd, palladium; TCR, T cell receptor; TRAV, TCR α‐chain V‐segment; TRBV, TCR β‐chain V‐segment