Regulation of CD1a surface expression and antigen presentation by invariant chain and lipid rafts.
In immature dendritic cells (DCs), CD1a is almost exclusively expressed at the cell surface and its membrane organization is poorly understood. In this study, we report that MHC class II, invariant chain (Ii), and CD9 molecules are coimmunoprecipitated with CD1a in immature DCs, and that CD1a/Ii colocalization is dependent on lipid raft integrity. In HeLa-CIITA cells CD1a expression leads to increased Ii trafficking to the cell surface, confirming the relevance of this association. Furthermore, silencing of Ii in DCs induces significant CD1a accumulation on the plasma membrane whereas the total CD1a expression remains similar to that of control cells. These data suggest that CD1a recycling is facilitated by the association with the Ii. The CD1a localization in lipid rafts has functional relevance as demonstrated by inhibition of CD1a-restricted presentation following raft disruption. Overall, these findings identify Ii and lipid rafts as key regulators of CD1a organization on the surface of immature DCs and of its immunological function as Ag-presenting molecule.
Sloma
Ivan
I
Institut National de la Santé et de la Recherche Médicale U662, Paris, France.
Zilber
Marie-Thérèse
MT
Vasselon
Thierry
T
Setterblad
Niclas
N
Cavallari
Marco
M
Mori
Lucia
L
De Libero
Gennaro
G
Charron
Dominique
D
Mooney
Nuala
N
Gelin
Catherine
C
D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D018949:Antigens, CD1 / Q000032:analysis / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D060245:Tetraspanin 29
D015703:Antigens, CD; D018949:Antigens, CD1; D000944:Antigens, Differentiation, B-Lymphocyte; C419393:CD1a antigen; C554869:CD9 protein, human; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; C045084:invariant chain