On the nature of signal 1 delivered to lymphocytes: A critical response to some considerations put forward in support of the quantum model of T cell activation.

The original Two Signal Model of lymphocyte activation stated that antigen-dependent lymphocyte cooperation is required for lymphocyte activation, whereas a single or a few antigen-specific lymphocytes can be inactivated by antigen. A virtue of this model is its ability to account for peripheral tolerance. Both the activation and inactivation of lymphocytes were envisaged to require the lymphocytes' antigen-specific receptors to interact with antigen, leading to signal 1. We consider here the proposition that the sensitivity to antigen concentration for the generation of signal 1, to support both differentiation processes, is the same. This situation optimizes the reliability of peripheral tolerance and minimizes the effects of lymphocyte inactivation in decreasing the diversity of the lymphocytes. We consider the broader implications of this Principle of Parsimonious Sensitivity in regulating the activity of lymphocytes.