title: Identification of the tetraspanin CD82 as a new barrier to xenotransplantation.
abstract: Significant immunological obstacles are to be negotiated before xenotransplantation becomes a clinical reality. An initial rejection of transplanted vascularized xenograft is attributed to Galα1,3Galβ1,4GlcNAc-R (Galα1,3-Gal)-dependent and -independent mechanisms. Hitherto, no receptor molecule has been identified that could account for Galα1,3-Gal-independent rejection. In this study, we identify the tetraspanin CD82 as a receptor molecule for the Galα1,3-Gal-independent mechanism. We demonstrate that, in contrast to human undifferentiated myeloid cell lines, differentiated cell lines are capable of recognizing xenogeneic porcine aortic endothelial cells in a calcium-dependent manner. Transcriptome-wide analysis to identify the differentially expressed transcripts in these cells revealed that the most likely candidate of the Galα1,3-Gal-independent recognition moiety is the tetraspanin CD82. Abs to CD82 inhibited the calcium response and the subsequent activation invoked by xenogeneic encounter. Our data identify CD82 on innate immune cells as a major "xenogenicity sensor" and open new avenues of intervention to making xenotransplantation a clinical reality.
authors.affiliation: Department of Cell Biology, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
authors.forename: Soad M
authors.initials: SM
authors.lastname: Saleh
authors.forename: Ranjit S
authors.initials: RS
authors.lastname: Parhar
authors.forename: Reem S
authors.initials: RS
authors.lastname: Al-Hejailan
authors.forename: Razan H
authors.initials: RH
authors.lastname: Bakheet
authors.forename: Hala S
authors.initials: HS
authors.lastname: Khaleel
authors.forename: Hanif G
authors.initials: HG
authors.lastname: Khalak
authors.forename: Anason S
authors.initials: AS
authors.lastname: Halees
authors.forename: Marya Z
authors.initials: MZ
authors.lastname: Zaidi
authors.forename: Brian F
authors.initials: BF
authors.lastname: Meyer
authors.forename: Gisella P
authors.initials: GP
authors.lastname: Yung
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Seebach
authors.forename: Walter
authors.initials: W
authors.lastname: Conca
authors.forename: Khalid S
authors.initials: KS
authors.lastname: Khabar
authors.forename: Kate S
authors.initials: KS
authors.lastname: Collison
authors.forename: Futwan A
authors.initials: FA
authors.lastname: Al-Mohanna
mesh_terms: D000818:Animals; D015153:Blotting, Western; D042783:Endothelial Cells / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D051861:Kangai-1 Protein / Q000276:immunology*; D018613:Microscopy, Confocal; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D051861:Kangai-1 Protein