A non-conserved amino acid variant regulates differential signalling between human and mouse CD28
CD28 superagonistic antibodies (CD28SAb) can preferentially activate and expand immunosuppressive
regulatory T cells (Treg) in mice. However, pre-clinical trials assessing
CD28SAbs for the therapy of autoimmune diseases reveal severe systemic inflammatory
response syndrome in humans, thereby implying the existence of distinct signalling abilities
between human and mouse CD28. Here, we show that a single amino acid variant within the
C-terminal proline-rich motif of human and mouse CD28 (P212 in human vs. A210 in mouse)