Advantage of higher-avidity CTL specific for Tax against human T-lymphotropic virus-1 infected cells and tumors

► We developed two Tax-specific CTLs with different avidity from HLA-A2 Tg mice. ► Higher avidity CTL (HCTL) had stronger affinity and expressed more TCRs on surface. ► HCTL could recognize latent amount of Tax detected only with a real-time PCR. ► HCTL selectively killed HTLV-1 infected human non-tumor target. ► This in vitro model suggests HCTL could be critical in limiting HTLV-1 infection. Strong CTL response can be observed and associated with the control of proviral load in human T-lymphotropic virus type 1 (HTLV-1) infection. However, there are few details with regard to how HTLV-1 specific CTLs work against HTLV-1 infected cells and adult T-cell leukemia cells (ATLs). In this study, using Tax-specific CTL lines with high- and low-functional avidity developed from HLA-A2-transgenic mice, we showed that higher avidity CTLs specific for Tax expressing larger numbers of TCRs and better binding strength to the antigen-HLA-A2 complex are much more efficient at eliminating HTLV-1 infected cells and, in particular, ATL tumor cells with the ability of recognizing a latent level of Tax product detected only with a real-time PCR. These findings suggest that such higher avidity CTLs specific for Tax in HTLV-1 could be responsible for preventing the development of HTLV-1 infection by detecting trace amount of antigens.