Figure 1. MHC cross-dressing can promote interaction between helper or regulatory CD4⁺ T cells and effector T cells.

Panel A shows how donor MHC class I cross-dressing of a recipient APC might promote cooperation between CD4⁺ T helper cells and CD8⁺ T effector cells by having self-MHC class II + donor peptide (indirect presentation) and donor MHC class I co-presented on the same APC (semi-direct presentation) (three cell cluster).

Panel B shows how simultaneous presentation of intact donor MHC molecules (semi-direct pathway) and self-MHC class II bound to a donor peptide (indirect pathway) or a self-peptide on the same recipient APC can promote interaction between regulatory CD4⁺ Tregs and effector CD4⁺ and CD8⁺ T cells. In this scenario, it is possible that Tregs can suppress effector T cells displaying the same self-MHC class II-peptide complex as recipient APCs (T-T interaction). In this setting, effector T cells are specific for donor MHC while Tregs are not donor specific but interact with self-MHC class II-peptide complexes on activated effector T cells.