Unique and common TCR repertoire features of Ni 2+ -, Co 2+ -, and Pd 2+ -specific human CD154 + CD4+ T cells.

Autor:	Riedel F; Dermatotoxicology Study Centre, German Federal Institute for Risk Assessment, Berlin, Germany.; Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany.; Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany., Aparicio-Soto M; Dermatotoxicology Study Centre, German Federal Institute for Risk Assessment, Berlin, Germany.; Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany., Curato C; Dermatotoxicology Study Centre, German Federal Institute for Risk Assessment, Berlin, Germany.; Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany., Münch L; Dermatotoxicology Study Centre, German Federal Institute for Risk Assessment, Berlin, Germany., Abbas A; Dermatotoxicology Study Centre, German Federal Institute for Risk Assessment, Berlin, Germany.; German Rheumatism Research Center (DRFZ), Berlin, Germany., Thierse HJ; Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany., Peitsch WK; Department of Dermatology and Phlebology, Vivantes Klinikum im Friedrichshain, Berlin, Germany., Luch A; Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany.; Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany., Siewert K; Dermatotoxicology Study Centre, German Federal Institute for Risk Assessment, Berlin, Germany.; Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany.
Jazyk:	angličtina
Zdroj:	Allergy [Allergy] 2023 Jan; Vol. 78 (1), pp. 270-282. Date of Electronic Publication: 2022 Sep 06.
DOI:	10.1111/all.15494
Abstrakt:	Background: Apart from Ni ²⁺ , Co ²⁺ , and Pd ²⁺ 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 Ni ²⁺ -, Co ²⁺ -, and Pd ²⁺ -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 NiSO 4 , CoCl 2 , and PdCl 2 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 Pd ²⁺ -specific T cells (mean 3.5%, n = 19), followed by Co ²⁺ - and Ni ²⁺ -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 Ni ²⁺ -specific TCR (28% of TCR) while Co ²⁺ and Pd ²⁺ -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 Ni ²⁺ -, Co ²⁺ -, and Pd ²⁺ -specific CD4+ T cells. Distinct TCR repertoire features underlie the frequent activation and cross-reactivity of human metal-specific T cells. (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze:	MEDLINE
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