T cell responses are governed by avidity and co‐stimulatory thresholds

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Abstract
We analyzed the avidity and CD28‐mediated co‐stimulatory requirements for the activation of T cells in vivo and in vitro. The strength of the T cell/antigen‐presenting cell interaction was varied by using altered peptide ligands for stimulation. Co‐stimulatory requirements were studied using T cells from CD28‐deficient mice. The results indicate that T cell activation is not an all‐or‐nothing event, but occurs in distinct steps. For each step, a certain avidity, co‐stimulatory threshold or both, must be met. Depending upon the strength of the interaction between the T cell receptor and the major histocompatibility complex/peptide and the presence of CD28 co‐stimulatory signals, T cells may undergo blast formation alone or proliferate or eventually both proliferate and differentiate to effector cells. Thus, T cell activation is governed by both avidity and co‐stimulatory thresholds.