Core Fucosylation of the T Cell Receptor Is Required for T Cell Activation

Abstract

CD4⁺ T cell activation promotes the pathogenic process of systemic lupus erythematosus (SLE). T cell receptor (TCR) complex are highly core fucosylated glycoproteins, which play important roles in T cell activation. In this study, we found that the core fucosylation of CD4⁺ T cells was significantly increased in SLE patients. Loss of core fucosyltransferase (Fut8), the sole enzyme for catalyzing the core fucosylation of N-glycan, significantly reduced CD4⁺ T cell activation and ameliorated the experimental autoimmune encephalomyelitis-induced syndrome in Fut8^-/- mice. T cell activation with OVA_323-339 loaded major histocompatibility complex II (pMHC-II) on B cell was dramatically attenuated in Fut8^-/-OT-II CD4⁺ T cells compared with Fut8^+/+OT-II CD4⁺ T cells. Moreover, the phosphorylation of ZAP-70 was significantly reduced in Fut8^+/+OT-II CD4⁺ T cells by the treatment of fucosidase. Our results suggest that core fucosylation is required for efficient TCR-pMHC-II contacts in CD4⁺ T cell activation, and hyper core fucosylation may serve as a potential novel biomarker in the sera from SLE patients.