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Su-Yi Tseng

Publications and source records attributed to Su-Yi Tseng.

4 recordsLinked to original sources

T cell-dendritic cell immunological synapses.

Dendritic cells (DCs) are myeloid lineage cells that are imprinted by their environment and that mature in response to microbial products. A crucial role of the DC is to impart this context-specific information to T cells as well as to present self and foreign MHC-peptide complexes through formation of an immunological synapse. The structure of the T cell-DC immunological synapse departs from the canonical structure formed with B cells or with supported planar bilayers in that it has multiple foci of T-cell receptor interactions rather than a central focus. Recent studies on model systems provide insight into the mechanisms and biological consequences of the unique T cell-DC synaptic patterns.

Animals↗

CD80 cytoplasmic domain controls localization of CD28, CTLA-4, and protein kinase Ctheta in the immunological synapse.

The binding of costimulatory ligand CD80 to CD28 or CTLA-4 on T cells plays an important role in the regulation of the T cell response. We have examined the role of the cytoplasmic domain of CD80 in murine T cell costimulation and its organization in the immunological synapse (IS). Removal of CD80 cytoplasmic tail decreased its effectiveness in costimulating T cell proliferative response and early IL-2 production in response to agonist MHC-peptide complexes. Immunofluorescent study showed a decreased tailless CD80 accumulation in the IS of naive T cells. The two forms of CD80 accumulated differently at the IS; the tailless CD80 was colocalized with the TCR whereas the full-length CD80 was segregated from the TCR. In addition, we showed that CD80, CD28, and protein kinase Ctheta colocalized in the presence or absence of the CD80 cytoplasmic tail. Thus, the cytoplasmic tail of CD80 regulates its spatial localization at the IS and that of its receptors and T cell signaling molecules such as protein kinase Ctheta, and thereby facilitates full T cell activation.

Animals↗

Naturally occurring human IgM antibody that binds B7-DC and potentiates T cell stimulation by dendritic cells.

A human IgM Ab, serum-derived human IgM 12 (sHIgM12), is identified that binds mouse and human dendritic cells (DC), inducing dramatic immunopotentiation following treatment of the mouse DC in vitro. Competition, transfection, and knockout studies identified the ligand on mouse DC as the costimulatory molecule family member B7-DC. Potent T cell responses are stimulated by Ag-pulsed DC treated with the sHIgM12 Ab in vitro and upon adoptive transfer of Ab-treated Ag-pulsed DC into animals. The multivalent structure of pentameric IgM provides the potential for cross-linking cell surface targets, endowing the soluble Abs with biological potential not normally associated with immune function. The ability of the sHIgM12 Ab to potentiate the immune response is dependent on the multimeric structure of IgM, as bivalent monomers do not retain this property. Furthermore, pretreatment of DC with IgM monomers blocks subsequent potentiation by intact IgM pentamers, an indication that cross-linking of B7-DC on the cell surface is critical for potentiation of Ag presentation. These findings imply that, in addition to known costimulatory roles, B7-DC can function as a receptor for signals delivered by cells expressing B7-DC ligands.

Adjuvants, Immunologic↗

T-cell activation: a multidimensional signaling network.

Naïve T cell activation requires the interactions of antigen receptors, adhesion molecules and co-stimulatory molecules. Antigen receptors and adhesion molecules are involved in spatio-temporal movement to form a stable immunological synapse. This stable junction interrupts T cell migration, and provides a platform for temporally regulated co-stimulatory receptor signaling spanning a period of days.

Animals↗