The T Cell Repertoires from Nickel Sensitized Joint Implant Failure Patients

Nickel (Ni(2+)) is one of the most common allergens, affecting around 10–15% of the general population. As the demand for orthopedic implant surgery rises, the number of surgical revisions due to joint implant failure also increases. There is evidence that some patients develop joint failure due to an immune response to a component of the implant, and we have found that Ni(2+) is an especially important cause. Hence, understanding the mechanisms by which Ni(2+) allergy induces joint implant failure becomes a critical research question. The structural basis of Ni(2+) activation of pathogenic T cells is still not clear. The purpose of this study was to characterize Ni(2+)-reactive T cell repertoires derived from the peripheral blood of joint failure patients due to Ni(2+) sensitization using single-cell sequencing techniques. We stimulated the proliferation of Ni(2+) -reactive T cells from two implant failure patients in vitro, and sorted them for single-cell VDJ sequencing (10× genomics). We identified 2650 productive V-J spanning pairs. Both TCR α chains and β chains were enriched. TRBV18 usage is the highest in the P7 CD4+ population (18.1%), and TRBV5-1 usage is the highest in the P7 CD8+ population (12.1%). TRBV19 and TRBV20-1 segments are present in a high percentage of both P7 and P9 sequenced T cells. Remarkably, the alpha and beta chain combination of TRAV41-TRBV18 accounts for 13.5% of the CD4+ population of P7 patient. Compared to current Ni specific T cell repertoire studies of contact dermatitis, the Vα and Vβ usages of these joint implant failure patients were different. This could be due to the different availability of self-peptides in these two different tissues. However, TRBV19 (Vβ17) was among frequently used TCR β chains, which are common in previous reports. This implies that some pathogenic T cells could be similar in Ni(2+) hypersensitivities in skin and joints. The alignment of the TCR CDR3β sequences showed a conserved glutamic acid (Glu) that could potentially interact with Ni(2+). The study of these Ni(2+) specific TCRs may shed light on the molecular mechanism of T cell activation by low molecular weight chemical haptens.