Response of Human T Cells to Tetanus Neurotoxin H-CC Sub-Domain: T Cell Cytokine Production and Activation Marker Induced by H-CC

Abstract

Tetanus is caused by the tetanus neurotoxin (TeNT), a 150 kDa single polypeptide molecule which is cleaved into active two-chain molecules composed of a 50 kDa N-terminal light (L) and a 100 kDa C-terminal heavy (H) chains. Fragment C is further subdivided into two subdomains: the proximal H-CN subdomain and the extreme carboxy subdomain, H-CC. H-CC is considered as an immunodominant part of TeNT and is responsible for TeNT binding activity to neurons. In the present study, we investigated the ability of recombinant H-CC(r H-CC) to induce T cell activation. Our results showed that recombinant H-CC has a stimulatory effect on IFN-gamma secretion by T cells after 48h co-incubation in the presence of anti-TLR-2 Ab. Also, Hcc can induce the expression of CD69 on T cells. Our finding indicated that stimulatory effects of H-CC on T cells are TLR-2 independent and anti-TLR-2 inhibitory antibody fails to neutralize H-CC stimulatory effects on T cells. Furthermore, H-CC is critical for immunogenic activity of TeNT and is able to induce T cells through TLR-2 independent pathway.