title: Tunneling nanotubes enable intercellular transfer of MHC class I molecules.
abstract: Carefully orchestrated intercellular communication is an essential prerequisite for an effective immune response. In recent years tunneling nanotubes (TNT) have emerged as a novel mechanism of cell-cell communication. These long membrane protrusions can establish cytoplasmic continuity between distant cells and enable the exchange of cellular components. In the present study we addressed the question whether these structures can facilitate the intercellular transfer of MHC class I molecules. We found a transmembrane HLA-A2-EGFP but not a soluble HLA-G1s-EGFP fusion protein to be effectively transferred between HeLa cells. Inhibition of actin polymerization significantly reduced the HLA-A2 transfer rate, indicating that transfer is dependent on tunneling nanotubes, whose de novo formation requires actin polymerization. Furthermore, overexpression of the nanotube-inducing protein LST1 promoted transfer of HLA-A2. Moreover, LST1 protein expression is enhanced in antigen presenting cells. Our results indicate that tunneling nanotubes can mediate transfer of MHC class I molecules between distant cells.
authors.affiliation: Department of Biology II, Ludwig-Maximilians-Universität München, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schiller
authors.forename: Johanna E
authors.initials: JE
authors.lastname: Huber
authors.forename: Kalliope N
authors.initials: KN
authors.lastname: Diakopoulos
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Weiss
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D022081:Cell Surface Extensions / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism*; D059951:HLA-G Antigens / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D058105:Polymerization / Q000187:drug effects; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D015789:HLA-A2 Antigen; D059951:HLA-G Antigens; D047908:Intracellular Signaling Peptides and Proteins; C093604:LST1 protein, human; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D014404:Tubulin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins