Toxicology and applied pharmacology 2017 05 26331() 69-75 pii 10.1016/j.taap.2017.05.020
T cell mediated hypersensitivity to nickel (Ni(2+)) is one of the most common causes of allergic contact dermatitis. Ni(2+) sensitization may also contribute to the failure of Ni(2+) containing joint implants, and revision to non-Ni(2+) containing hardware can be costly and debilitating. Previously, we identified Ni(2+) mimotope peptides, which are reactive to a CD4(+) T cell clone, ANi2.3 (Vα1, Vβ17), isolated from a Ni(2+) hypersensitive patient with contact dermatitis. This T cell is restricted to the major histocompatibility complex class II (MHCII) molecule, Human Leukocyte Antigen (HLA)-DR52c (DRA, DRB3*0301). However, it is not known if Ni(2+) induced T cell responses in sensitized joint replacement failure patients are similar to subjects with Ni(2+) induced contact dermatitis. Here, we generated DR52c/Ni(2+) mimotope tetramers, and used them to test if the same Ni(2+) T cell activation mechanism could be generalized to Ni(2+) sensitized patients with associated joint implant failure. We confirmed the specificity of these tetramers by staining of ANi2.3T cell transfectomas. The DR52c/Ni(2+) mimotope tetramer detected Ni(2+) reactive CD4(+) T cells in the peripheral blood mononuclear cells (PBMC) of patients identified as Ni(2+) sensitized by patch testing and a positive Ni(2+) LPT. When HLA-typed by a DR52 specific antibody, three out of four patients were DR52 positive. In one patient, Ni(2+) stimulation induced the expansion of Vβ17 positive CD4(+) T cells from 0.8% to 13.3%. We found that the percentage of DR52 positivity and Vβ17 usage in Ni(2+) sensitized joint failure patients are similar to Ni sensitized skin allergy patients. Ni(2+) independent mimotope tetramers may be a useful tool to identify the Ni(2+) reactive CD4(+) T cells.