Genetic, dynamic and functional definition of the efficency of the anti-viral T cell response

In infection with the human T cell leukaemia virus (HTLV-I), there is a powerful T cell immune response to one of the viral proteins, called Tax. We have obtained evidence that the strength of this immune response determines the "set point" of HTLV-I load in the blood, which can vary between HTLV-I-infected people by more than 1000 times, but is constant in each infected person over time. Our evidence is derived from experimental data on genetic variation in the host and in HTLV-I, cellular immunology, and DNA expression microarrays. We have used dynamical approaches a) to reconcile the evidence of persistent HTLV-I replication with the observed conservation of HTLV-I sequence; b) to suggest a reason for the apparent threshold in HTLV-I load above which many people develop chronic inflammatory diseases; c) to explain the observed variation between individuals in the frequency of anti-HTLV-I T cells, and d) to test the consequences of HTLV-I-induced T cell death on the control of HTLV-I replication. The aims of this work are to define the concept of antiviral "T cell efficiency" in genetic, dynamical and functional terms, and to test experimentally whether this "efficiency" determines the outcome of HTLV-I infection.