Figure 1. Context dependent CTL activation.

Migratory DCs capture antigen and traffic to the LN where they can present to CD4⁺ T cells and transfer antigen to LN-resident DCs. (A) In the case of self-antigens (blue), CD4⁺ T cells are not activated and thus LN-resident DCs capable of cross presentation are not licensed or conditioned to provide proper costimulation to potentially autoreactive CTLs, leading to no activation or AICD. (B) In the context of an acute pathogenic insult, abundant foreign antigen (red) and PRR engagement leads to CD4⁺ activation and proper conditioning of LN-resident DCs via CD40:CD40L interactions. Ultimately, cognate CD8⁺ T cells undergo robust expansion and memory formation due to optimal costimulation. (C) Rare tumor antigens (purple) relative to autoantigens (blue) and lack of PRR activation leads to incomplete costimulation. The resulting helpless or exhausted CTLs may be insufficient to control the tumor. Some CTLs might receive all necessary cues and form proper memory; however, the clonal diversity of the effective CTL response is dramatically decreased and may lead to tumor escape.