title: Mechanical interactions between dendritic cells and T cells correlate with T cell responsiveness.
abstract: Ag recognition is achieved through the communication across intercellular contacts between T cells and APCs such as dendritic cells (DC). Despite remarkable progress in delineating detailed molecular components at the intercellular contacts, little is known about the functional roles of physical cross-junctional adhesion between T and DC in shaping T cell responses. In addition, the mechanisms underlying sensitivity and specificity of Ag discrimination by T cells at intercellular contacts remain to be elucidated. In this study, we use single-cell force spectroscopy to probe the mechanical interactions between DC and T cells in response to stimulation with a panel of altered peptide ligands. The results show that intercellular interactions of DC-T cell conjugates exhibited different ranges of interaction forces in peptide-dependent manners that match the ability of the peptides to activate T cells. Elevated calcium mobilization and IL-2 secretion by T cells were only promoted in response to antigenic peptides that induce strong interaction forces, suggesting that mechanically stable DC-T cell contacts are crucial for driving T cell activation. Strong interactions were not solely dependent on cell-surface molecules such as TCRs and the adhesion molecule LFA-1, but were also controlled by cytoskeletal dynamics and the integrity of membrane lipid rafts. These data provide novel mechanical insights into the effect of Ag affinity on intercellular contacts that align with T cell responsiveness.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, 138648 Singapore. lim_tong_seng@immunol.a-star.edu.sg
authors.forename: Tong Seng
authors.initials: TS
authors.lastname: Lim
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mortellaro
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
authors.forename: Günter J
authors.initials: GJ
authors.lastname: Hämmerling
authors.forename: Paola
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000172:deficiency / Q000378:metabolism; D003599:Cytoskeleton / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000378:metabolism / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: C489629:H-2A(b) antigen, mouse; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; C111390:OVA 323-339; D010446:Peptide Fragments; D010455:Peptides; D010047:Ovalbumin; D002784:Cholesterol; D002118:Calcium