title: Costimulation and endogenous MHC ligands contribute to T cell recognition.
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-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.
authors.affiliation: The Howard Hughes Medical Institute and The Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wülfing
authors.forename: Cenk
authors.initials: C
authors.lastname: Sumen
authors.forename: Michael D
authors.initials: MD
authors.lastname: Sjaastad
authors.forename: Lawren C
authors.initials: LC
authors.lastname: Wu
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D020013:Calcium Signaling; D002450:Cell Communication / Q000276:immunology*; D016764:Cell Polarity; D002478:Cells, Cultured; D005802:Genes, MHC Class II; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D007152:Immunologic Capping; D007519:Isoantigens / Q000276:immunology*; D008024:Ligands; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D018448:Models, Immunological; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D017634:Self Tolerance / Q000276:immunology*; D014162:Transfection
chemical_list: D001324:Autoantigens; D018106:CD28 Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007519:Isoantigens; D008024:Ligands; D008164:Luminescent Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D046911:Macromolecular Substances; D008565:Membrane Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins