In:
Allergy, Wiley, Vol. 78, No. 1 ( 2023-01), p. 270-282
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0105-4538
,
1398-9995
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2003114-2
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