title: The adaptor protein Bam32 in human dendritic cells participates in the regulation of MHC class I-induced CD8+ T cell activation.
abstract: The B lymphocyte adaptor molecule of 32 kDa (Bam32) is strongly induced during the maturation of dendritic cells (DC). Most known functions of Bam32 are related to the signaling of the B cell receptor for Ag. Because DC do not express receptors specific for Ags, we aim at characterizing the role of Bam32 in human monocyte-derived DC in this study. Our results show that binding of allogeneic T cells to mature DC causes accumulation of Bam32 on the contact sites and that this translocation is mimicked by Ab-mediated engagement of MHC class I. Silencing of Bam32 in mature monocyte-derived DC results in an enhanced proliferation of CD8(+) T cells in an Ag-specific T cell proliferation assay. Further studies identify galectin-1 as an intracellular binding partner of Bam32. Regulating immune responses via regulatory T cell (Treg) modulation is one of the many immunological activities attributed to galectin-1. Therefore, we assayed mixed leukocyte reactions for Treg expansion and found fewer Treg in reactions stimulated with DC silenced for Bam32 compared to reactions stimulated with DC treated with a nontarget control. Based on our findings, we propose a role for Bam32 in the signaling of MHC class I molecules in professional Ag-presenting DC for the regulation of CD8(+) T cell activation. It is distinct from that of MHC class I recognized by CD8(+) T cells leading to target [corrected] cell death. Thus, our data pinpoint a novel level of T cell regulation that may be of biological relevance.
authors.affiliation: Department of Dermatology, Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ortner
authors.forename: Daniela
authors.initials: D
authors.lastname: Grabher
authors.forename: Martin
authors.initials: M
authors.lastname: Hermann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Susanne
authors.initials: S
authors.lastname: Hofer
authors.forename: Christine
authors.initials: C
authors.lastname: Heufler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology* / Q000378:metabolism; D017951:Antigen Presentation / Q000276:immunology; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C486555:DAPP1 protein, human; D015395:Histocompatibility Antigens Class I