Figure 1. A new dynamic model of three cell interactions. (A) The passive “three-cell interaction” model. A CD4⁺ T helper cell activated by a dendritic cells (DC) delivers interleukin-2 (IL-2) required for the activation of a CD8⁺ T cell that recognizes the same antigen presented by the DC. (B) The dynamic model of “sequential two-cell interaction by DCs.” The cross-priming DC gets activated (licensed) by antigen-specific CD4⁺ T helper cell through CD40-CD40L interactions, and then acquires the ability to directly prime CTLs. (C) The dynamic model of “sequential two-cell interactions by CD4⁺ T cells-APCs.” CD4⁺ T cells can acquire molecules (particularly pMHCI) from APCs and thus can directly stimulate CTL responses. (D) A new dynamic model of three cell interactions. The cross-priming DC first interacts with antigen-specific CD4⁺ T helper cell (a crucial step in CTL responses), resulting in DC licensing and CD4⁺ T cell activation (priming). Cognate CD8⁺ CTLs can then receive helper or stimulatory signals not only from DC-CD4⁺ T-cell clusters, but also separately from fully licensed DCs and primed CD4⁺ T cells, even after their dissociation from DC-CD4⁺ T-cell clusters.