Using DR52c/Ni{sup 2+} mimotope tetramers to detect Ni{sup 2+} reactive CD4{sup +} T cells in patients with joint replacement failure
T cell mediated hypersensitivity to nickel (Ni{sup 2+}) is one of the most common causes of allergic contact dermatitis. Ni{sup 2+} sensitization may also contribute to the failure of Ni{sup 2+} containing joint implants, and revision to non-Ni{sup 2+} containing hardware can be costly and debilitating. Previously, we identified Ni{sup 2+} mimotope peptides, which are reactive to a CD4{sup +} T cell clone, ANi2.3 (Vα1, Vβ17), isolated from a Ni{sup 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{sup 2+} induced T cell responses in sensitized joint replacement failure patients are similar to subjects with Ni{sup 2+} induced contact dermatitis. Here, we generated DR52c/Ni{sup 2+} mimotope tetramers, and used them to test if the same Ni{sup 2+} T cell activation mechanism could be generalized to Ni{sup 2+} sensitized patients with associated joint implant failure. We confirmed the specificity of these tetramers by staining of ANi2.3 T cell transfectomas. The DR52c/Ni{sup 2+} mimotope tetramer detected Ni{sup 2+} reactive CD4{sup +} T cells in the peripheral blood mononuclear cells (PBMC) of patients identified as Ni{sup 2+} sensitized by patch testing and a positive Ni{sup 2+} LPT. When HLA-typed by a DR52 specific antibody, three out of four patients were DR52 positive. In one patient, Ni{sup 2+} stimulation induced the expansion of Vβ17 positive CD4{sup +} T cells from 0.8% to 13.3%. We found that the percentage of DR52 positivity and Vβ17 usage in Ni{sup 2+} sensitized joint failure patients are similar to Ni sensitized skin allergy patients. Ni{sup 2+} independent mimotope tetramers may be a useful tool to identify the Ni{sup 2+} reactive CD4{sup +} T cells. - Highlight: • Nickel hypersensitive patients with implant failure are dominantly DR52 positive. • These patients may have similar TCR beta chain usage to that of contact dermatitis. • The nickel mimotope tetramers are a tool to identify the nickel reactive CD4{sup +} T cells.