Direct Activation of Human Dendritic Cells by Particle-Bound but Not Soluble MHC Class II Ligand

• DOI: 10.1371/journal.pone.0063039
• Publication Date: 2013-05-03T04:13:32Z
• Authors: Renato B. Baleeiro; Karl-Heinz Wiesmü...; Lars Dähne; Jürgen Lademann; José A. Barbuto; Peter Walden
• Keywords: 0301 basic medicine; Science; T-Lymphocytes; Q; R; Intracellular Space; 500; Cell Differentiation; Dendritic Cells; 3. Good health; Phosphotransferases (Alcohol Group Acceptor); 03 medical and health sciences; Phenotype; Calmodulin; Solubility; Malaria Vaccines; Medicine; Humans; Amino Acid Sequence; Calcium Signaling; Research Article

Dendritic cells (DCs) are key activators of cellular immune responses through their capacity to induce naïve T and sustained effector cell responses. This is a function superior efficiency antigen presentation via MHC class I II molecules, the expression co-stimulatory surface molecules cytokines. Maturation DCs induced by microbial factors pattern recognition receptors such as Toll-like receptors, pro-inflammatory cytokines or cognate interaction with CD4+ cells. Here we show that, unexpectedly, PanDR helper epitope PADRE, generic presented large fraction HLA-DR alleles, when delivered in particle-bound form maturation human DCs. The that received PADRE displayed all features fully mature DCs, high CD80, CD86, CD83, MHC-II molecule HLA-DR, secretion levels biologically active IL-12 (IL-12p70) induction vigorous proliferation Furthermore, was shown involve sphingosine kinase, calcium signaling from internal sources downstream MAP kinase p72syk pathways, finally activation transcription factor NF-κB. Based on our findings, propose may be used DC activator DC-based vaccines.