B cell lipid rafts regulate both peptide-dependent and peptide-independent APC-T cell interaction.
Formation of an immunological synapse (IS) between APCs and T CD4(+) lymphocytes is a key event in the initiation and the termination of the cognate immune response. We have analyzed the contribution of the APC to IS formation and report the implication of the actin cytoskeleton, the signaling proteins and the lipid rafts of B lymphocytes. Recruitment of MHC class II molecules to the IS is concomitant with actin cytoskeleton-dependent B cell raft recruitment. B cell actin cytoskeleton disruption abrogates both IS formation and T cell activation, whereas protein kinase C inhibition only impairs T cell activation. Pharmacological B cell lipid raft disruption inhibited peptide-dependent T lymphocyte activation and induced peptide-independent but HLA-DR-restricted APC-T cell conjugate formation. Such peptide-independent conjugates did not retain the ability to activate T cells. Thus, B cell lipid rafts are bifunctional by regulating T cell activation and imposing peptide stringency.
Setterblad
Niclas
N
Institut National de la Santé et de la Recherche Médicale Unité 396, Institut Universitaire d'Hématologie, Hôpital St.-Louis, Paris, France.
Bécart
Stéphane
S
Charron
Dominique
D
Mooney
Nuala
N
D000199:Actins / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000648:ultrastructure; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D002450:Cell Communication; D002478:Cells, Cultured / Q000276:immunology / Q000648:ultrastructure; D003505:Cyclodextrins / Q000494:pharmacology; D003599:Cytoskeleton / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D006825:Hybridomas / Q000276:immunology / Q000648:ultrastructure; D007365:Intercellular Junctions / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D021962:Membrane Microdomains / Q000502:physiology*; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction; D037182:T-Cell Antigen Receptor Specificity; D013745:Tetanus Toxoid / Q000276:immunology; D047392:beta-Cyclodextrins
D000199:Actins; D015704:CD4 Antigens; D003505:Cyclodextrins; D004791:Enzyme Inhibitors; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007376:Interleukin-2; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D013745:Tetanus Toxoid; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C093151:tetanus toxoid (830-843); D011493:Protein Kinase C