Costimulation and endogenous MHC ligands contribute to T cell recognition

Top Cited Papers
Publisher Website
Google Scholar
Abstract
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 II molecule, I-Ek, 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 II (agonist pMHC class II) complexes can initiate T cell activation, endogenous pMHC class II complexes also appeared to accumulate. To test this directly, we labeled a “null” pMHC class II 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.