Human vascular endothelial cells process and present autoantigen to human T cell lines.
The effectiveness of cultured human umbilical vein endothelial cells as accessory cells for T cell activation has been investigated using T cell clones and lines derived from patients with myasthenia gravis which were specific for different epitopes on the alpha subunit of the human acetylcholine receptor. The endothelial cells were induced with IFN-gamma to express HLA-DR and -DQ at high and low levels respectively. They could then efficiently present specific peptides of the alpha subunit to an HLA-DR- and an HLA-DQw5-restricted T cell line. They could also process epitopes for both T cell lines from the full-length recombinant alpha subunit (r1-437) of the human acetylcholine receptor, where the known epitopes are 80 amino acid residues apart. The endothelial presentation of r1-437, but not of the peptides, was sensitive to chloroquine inhibition. Presentation appeared slightly less efficient (by 1.5- to 3.0-fold) with endothelial cells than with presenting cells from peripheral blood. This may reflect differences in accessory signalling since mAb blocking studies suggested that ligands for CD28 provided important accessory signalling by peripheral blood presenting cells while LFA-3 was used by endothelial cells.
Savage
C O
CO
Center for Clinical Research in Immunology and Signalling, Medical School, University of Birmingham, UK.
Brooks
C J
CJ
Harcourt
G C
GC
Picard
J K
JK
King
W
W
Sansom
D M
DM
Willcox
N
N
D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology; D018106:CD28 Antigens / Q000276:immunology; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology; D009157:Myasthenia Gravis / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014471:Umbilical Veins
D015703:Antigens, CD; D001324:Autoantigens; D018122:B7-1 Antigen; D018106:CD28 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D000939:Epitopes; D006683:HLA-DQ Antigens; C094373:HLA-DQw5 antigen; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011950:Receptors, Cholinergic; D007371:Interferon-gamma; D002738:Chloroquine