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Title

Identification of the tetraspanin CD82 as a new barrier to xenotransplantation

Authors
Saleh, Soad M
Parhar, Ranjit S
Al-Hejailan, Reem S
Bakheet, Razan H
Khaleel, Hala S
Khalak, Hanif G
Halees, Anason S
Zaidi, Marya Z
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Published in Journal of Immunology. 2013, vol. 191, no. 5, p. 2796-805
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.
Keywords AnimalsAntigens, CD82/immunologyBlotting, WesternEndothelial Cells/immunologyFlow CytometryFluorescent Antibody TechniqueGraft Rejection/immunologyHumansMicroscopy, ConfocalReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionSwineTransplantation, Heterologous/immunology
Identifiers
PMID: 23872050
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Article (Published version) (1.7 MB) - public document Free access
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Research group Groupe Seebach Jorg Dieter (transplantation et immunologie) (856)
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SALEH, Soad M et al. Identification of the tetraspanin CD82 as a new barrier to xenotransplantation. In: Journal of Immunology, 2013, vol. 191, n° 5, p. 2796-805. https://archive-ouverte.unige.ch/unige:43389

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Deposited on : 2014-12-15

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