Figure 3.

Peripheral T cell repertoires available to respond to non/self- and self-antigens are shaped according to the TCR–pMHC affinities of individual T cells. (A) After thymic selection, CD8 T cells specific for non-self (foreign) antigens express TCRs that span the entire physiological range from low (100 μM) to high (1 μM) affinity (depicted as colored arcs). In these non-self-specific repertoires, a large proportion (depicted as dark blue gradients) of T cells bear TCRs of intermediate to high-affinity TCRs (orange-red arcs). (B) Due to self-tolerance mechanisms, most but not all self/tumor antigen-specific T cells of high-affinity TCRs are deleted (red arcs). Consequently, T cell repertoires specific for self/tumor antigens are mainly composed (dark blue gradients) of low affinities (yellow arc). (C) T cells recognizing neoantigens are not deleted by self-tolerance mechanisms, since tumor-specific mutations generating neoantigens are “non-self like” epitopes. Thus, the repertoire of neoantigen-specific T cells is composed of increased proportions (dark blue gradients) of tumor-specific and high affinities TCRs (red arc).