Complement C3b fragment covalently linked to tetanus toxin increases lysosomal sodium dodecyl sulfate-stable HLA-DR dimer production.
Processing and presentation of covalently linked C3b-tetanus toxin (TT) complexes, as compared to unlinked C3b + TT, lead to increased T cell proliferation. The aim of this study was to analyze the effect of coupling C3b to TT on the efficiency of TT peptide loading on HLA-DR1 molecules. In the Epstein-Barr virus-transformed B cell line HOM 2, we detected a significant increase of sodium dodecyl sulfate (SDS)-stable major histocompatibility complex (MHC) class II molecules after exposure to C3b-TT as compared to unlinked C3b and TT. The ratio of compact form/unbound form (C/U ratio) obtained with C3b-TT as antigen (Ag) is about twice that obtained with uncomplexed TT + C3b as Ag. Similar results were obtained using HLA-DR1-transfected fibroblasts that do not express C3b complement receptors, indicating that the SDS-stable HLA-DR1 increase did not result simply from C3b opsonization but rather from a direct effect of C3b-TT linkage on peptide generation. Exposure of HOM 2 cells to C3b-TT resulted in an increase in concentration of SDS-stable HLA-DR molecules in lysosomes but not in endosomes. Thus, C3b attachment to Ag induces a redistribution of peptide/MHC complex which results in a higher efficiency of Ag presentation by MHC class II molecules.
Serra
V A
VA
Département de Biologie Moléculaire et Structurale, CEA, INSERM U238, Université Joseph Fourier, Grenoble, France.
Cretin
F
F
Pépin
E
E
Gabert
F M
FM
Marche
P N
PN
D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001692:Biological Transport; D002461:Cell Line, Transformed; D003179:Complement C3b / Q000276:immunology*; D003902:Detergents / Q000494:pharmacology; D019281:Dimerization; D015798:HLA-DR1 Antigen / Q000096:biosynthesis*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D011485:Protein Binding; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013744:Tetanus Toxin / Q000276:immunology*; D014162:Transfection
D000944:Antigens, Differentiation, B-Lymphocyte; D003902:Detergents; D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; D013744:Tetanus Toxin; C045084:invariant chain; D012967:Sodium Dodecyl Sulfate; D003179:Complement C3b