Presentation of antagonist peptides to naive CD4⁺ T cells abrogates spatial reorganization of class II MHC peptide complexes on the surface of dendritic cells

By using dendritic cells (DCs) transduced with retroviruses encoding covalent A^bβ/peptide fusion proteins tagged with fluorescent proteins, we followed the relocation of class II MHC molecules loaded with agonist or null peptides during the onset of activation of naive and effector CD4⁺ T cells. Clusters of T cell receptor (TCR)/CD3 complex formed in parallel with clusters of agonist class II MHC/peptide complexes on the surface of DCs. However, activation of naive but not effector T cells was accompanied by expulsion of the null class II MHC/peptide complexes from the T cell-DC interface. These effects were perturbed in the presence of exogenously supplied antagonist peptide. These results suggest that interference with selective relocation of agonist and null MHC/peptide complexes in the immunological synapse contributes to the inhibitory effect of antagonist peptides on the response of naive CD4⁺ T cells to agonist ligands.