Tetraspanins CD9 and CD81 are molecular partners of trimeric FcɛRI on human antigen-presenting cells.
BACKGROUND
Most functions of tetraspanins are not related to cell-surface receptor ligand binding, but are mediated by direct interactions with their partner proteins. Functions of trimeric FcɛRI, expressed by antigen-presenting cells (APCs), range from amplification of allergic inflammatory reactions to their active suppression. Cell-type-specific protein-protein interactions might play a role in the regulation of these bidirectional tasks. Therefore, we intended to study the interactions of trimeric FcɛRI with tetraspanins.


METHODS
The expression levels of tetraspanins CD9, CD37, CD53, CD63, CD81, CD82, and CD151 on skin dendritic cells of atopic dermatitis (AD) patients or healthy individuals were detected by flow cytometry. Tetraspanin expression on FcɛRI(pos) and FcɛRI(neg) monocyte subpopulations was evaluated. Flow cytometry, confocal microscopy, immunoprecipitation, and immunoblotting experiments were performed to observe the relationship between tetraspanins CD9 and CD81 and FcɛRI. Furthermore, plate stimulation experiments were performed, and cytokines in the supernatants were detected.


RESULTS
We found that human FcɛRI(pos) APCs expressed high amounts of tetraspanins and that the tetraspanins CD9 and CD81 were associated with FcɛRI. Concomitant activation of FcɛRI and CD9 on human monocytes increased FcɛRI-mediated cytokine release.


CONCLUSIONS
Taken together, we show for the first time that CD9 and CD81 act as molecular partners of trimeric FcɛRI on human APC, which might be of importance in allergic diseases such as AD.
Department of Dermatology and Allergy, University of Bonn Medical, Bonn, Germany.
W M
WM
Peng
C F
CF
Yu
W
W
Kolanus
A
A
Mazzocca
T
T
Bieber
S
S
Kraft
N
N
Novak
D000938:Antigen-Presenting Cells / Q000737:chemistry* / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000737:chemistry*; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D011485:Protein Binding; D017455:Receptors, IgE / Q000032:analysis / Q000378:metabolism*; D012867:Skin / Q000473:pathology; D060225:Tetraspanin 28; D060245:Tetraspanin 29
D015703:Antigens, CD; C554798:CD81 protein, human; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D017455:Receptors, IgE; D060225:Tetraspanin 28; D060245:Tetraspanin 29