Costimulation and endogenous MHC ligands contribute to T cell recognition

To initiate an immune response, key receptor-ligand pairs must cluster in "immune synapses" at the T cell-antigen-presenting cell (APC) interface. We visualized the accumulation of a major histocompatibility complex (MHC) class 11 molecule, I-E-k, at a T cell-B cell interface and found it was dependent on both antigen recognition and costimulation. This suggests that costimulation-driven active transport of T cell surface molecules helps to drive immunological synapse formation. Although only agonist peptide-MHC class 11 (agonist pMHC class 11) complexes can initiate T cell activation, endogenous pMHC class 11 complexes also appeared to accumulate. To test this directly, we labeled a "null" pMHC class 11 complex and found that, although it lacked major TCR contact residues, it could be driven into the synapse in a TCR-dependant manner. Thus, low-affinity ligands can contribute to synapse formation and T cell signaling.