Unique and common TCR repertoire features of Ni²⁺-, Co²⁺-, and Pd²⁺-specific human CD154 + CD4+ T cells | Unique and common TCR repertoire features of Ni2+‐, Co2+‐, and Pd2+‐specific human CD154 + CD4+ T cells
2023
Riedel, Franziska | Aparicio-Soto, Marina | Curato, Caterina | Münch, Lucas | Abbas, Amro | Thierse, Hermann-Josef | Peitsch, Wiebke K. | Luch, Andreas | Siewert, Katherina
Abstract 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 α? 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??M. 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 ?-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.
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出版者 Blackwell Munksgaard
ISSN 1398-9995 | 0105-4538