Figure 5.

Proposed mechanism for the role of aberrant protein deimination in an autoimmune response to brain injury. TBI-induced calcium excitotoxicity hyperactivates PAD resulting in an abnormal pattern of protein deimination. Cells of the adaptive immune system process the modified proteins to reveal antigenic epitopes created by deimination. Antigen presentation and T-cell activation subsequently lead to the activation of B-cells for the production of autoantibodies and chronic neuroinflammation. It is proposed that these mechanisms contribute to long-term pathologies that can result from TBI. Potential therapeutic interventions that inhibit protein deimination and T-cell and B-cell activation are depicted with red lines.