Figure 2.

Mechanisms for metal presentation to helper T-cells. (A) Antigen-presenting cells (APCs) digest endogenous or exogenous proteins, and the digested peptides can compete for the binding groove of major histocompatibility complex (MHC) molecules forming a MHC:peptide (MP) complex, which are then transported to the cell surface. Released metal ions from the implant can cross-link the MP complex (forming MHC:peptide:metal (MPM) complex) with T-cell receptors (TCRs), leading to helper T-cell activation; (B) Preformed metal–protein complexes are presented by APCs and recognized by TCRs, resulting in helper T-cell activation. Activated T-cells excrete cytokines that can recruit and activate macrophages. However, involvement of B-cells and antibodies in ALVAL has not been determined. Created with BioRender.com.