Signalling via MHC class II molecules modifies the composition of GEMs in APC.
Major histocompatibility complex (MHC) class II molecules are responsible for peptide presentation to helper T lymphocytes and as such play an essential role in the immune response. These molecules transmit intracellular signals leading to diverse consequences in B lymphocytes including proliferation and apoptosis. Recent studies have revealed that glycolipid enriched membrane microdomains (GEMs) behave as signalling platforms for a variety of lymphocyte receptors. We have quantified human leucocyte antigen (HLA)-DR molecules localized in GEMs in human B lymphocytes. Use of a model imitating the interaction of HLA-DR with a T-cell receptor (TCR) modified the constituents of the HLA-DR-enriched GEMs. Confocal microscopy demonstrated a recruitment of HLA-DR and the ganglioside GM1 at the site of HLA-DR interaction with the stimulating ligand. Moreover, cholesterol depletion efficiently impaired this recruitment. Co-localizing proteins detected in HLA-DR-enriched GEMs include protein kinase C (PKC)-delta and actin. These data reveal that MHC class II antigens are localized in GEMs in mature human B lymphocytes and indicates that the formation of the immunological synapse regulates the composition of HLA-DR enriched GEMs in the antigen presenting cell (APC).
Setterblad
N
N
INSERM U396, Institut Biomedical des Cordeliers, 15, rue de l'Ecole de Médecine, 75006 Paris, France.
Becart
S
S
Charron
D
D
Mooney
N
N
D000199:Actins / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007527:Isoenzymes / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology*; D011493:Protein Kinase C / Q000276:immunology; D051745:Protein Kinase C-delta; D015398:Signal Transduction / Q000276:immunology*
D000199:Actins; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007527:Isoenzymes; D002784:Cholesterol; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta