Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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-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 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-dependent manner. Thus, low-affinity ligands can contribute to synapse formation and T cell signaling.

Original publication




Journal article


Nat immunol

Publication Date





42 - 47


Animals, Autoantigens, B-Lymphocytes, CD28 Antigens, Calcium Signaling, Cell Communication, Cell Polarity, Cells, Cultured, Genes, MHC Class II, Genes, Reporter, Green Fluorescent Proteins, Histocompatibility Antigens Class II, Imaging, Three-Dimensional, Immunologic Capping, Isoantigens, Ligands, Luminescent Proteins, Lymphocyte Activation, Lymphocyte Function-Associated Antigen-1, Macromolecular Substances, Membrane Proteins, Mice, Microscopy, Fluorescence, Microscopy, Video, Models, Immunological, Peptide Fragments, Protein Transport, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins, Self Tolerance, Transfection