Fig. 3

Effect of p12/p8 on cytotoxic T-cells (CTLs). Cytotoxic CD8 T-cells (CTL) recognize target cells bearing an appropriate antigen-MHC I complex via the T-cell receptor (TCR). CTLs carry out target cell killing by releasing the cytotoxic proteins, granzyme B and perforin. Both p12 and p8 expression are important for HTLV-1 inhibition of CTL killing. By inducing the proteasome degradation of immature MHC I, p12 decreases MHC I surface expression, reducing antigen presentation to CTLs. In addition, the reduction of ICAM-1 expression in infected cells further reduces cell adhesion. The p8 protein enhances the number and length of cellular conduits between T-cells, allowing for the transfer of target cell proteins to other cells, including p8 itself. Transferred p8 could alter intracellular signaling and dampen TCR signaling to inhibit CTL killing. The p8 protein also promotes T-cell adhesion through lymphocyte function-associated antigen-1 (LFA-1) clustering and by enhancing the formation of cell-to-cell contacts promoting viral transmission