Figure 1: Comparison of the T cell repertoires available to respond to self- and foreign-antigen. Developing T cells generate T cell receptors that range from very weak to very strong self-reactivity. Negative selection eliminates thymocytes bearing a TCR that responds to self-antigen with an affinity that is above the negative selection threshold. The remaining fraction constitutes the peripheral repertoire. For most foreign-antigens, the peripheral repertoire contains naïve T cells that cover the entire affinity spectrum from very weak to very strong reactivity (indicated in green and yellow). The dashed line indicates the threshold for stimulating an effector response in peripheral T cells.

It is important to consider that peripheral T cells differ in their level of self-reactivity and that two T cell clones with similar reactivity to a foreign ligand could substantially differ in their auto-reactive potential, as depicted in orange and blue, for two examples of T cell clones. Thus, when a cell like the one shown in blue would become activated during an infection, it would not cause autoimmunity as its affinity for self is below the peripheral activation threshold. This is different for the orange cell which is above the threshold and whose activation can cause autoimmunity. Thus, the orange cell represents the low affinity auto-reactive T cells referred to in the text.