A non-conserved amino acid variant regulates differential signalling between human and mouse CD28.

ABSTRACT: 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) regulates CD28-induced NF-κB activation and pro-inflammatory cytokine gene expression. Moreover, this Y²⁰⁹APP²¹² sequence in humans is crucial for the association of CD28 with the Nck adaptor protein for actin cytoskeleton reorgani

SUBMITTER: Porciello N 

PROVIDER: S-EPMC5852078 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature