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

• DOI: 10.1111/all.15494
• Publication Date: 2022-08-25T12:00:01Z
• Authors: Franziska Riedel; Marina Aparicio‐Soto; Caterina Curato; Lucas Münch; Amro Abbas; Hermann‐Josef Thi...; Wiebke K. Peitsch; Andreas Luch; Katherina Siewert
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; 03 medical and health sciences; Receptors, Antigen, T-Cell, alpha-beta; Leukocytes, Mononuclear; Humans; Histidine; Complementarity Determining Regions

AbstractBackgroundApart 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.MethodsHere, 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.ResultsPeripheral 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.ConclusionsInduced 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.