Using DR52c/Ni mimotope tetramers to detect Ni reactive CD4 T cells in patients with joint replacement failure.

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