MHC class II molecules, cathepsins, and La/SSB proteins in lacrimal acinar cell endomembranes.
Sjögren's syndrome is a chronic autoimmune disease affecting the lacrimal glands and other epithelia. It has been suggested that acinar cells of the lacrimal glands provoke local autoimmune responses, leading to Sjögren's syndrome when they begin expressing major histocompatibility complex (MHC) class II molecules. We used isopycnic centrifugation and phase partitioning to resolve compartments that participate in traffic between the basolateral membranes and the endomembrane system to test the hypothesis that MHC class II molecules enter compartments that contain potential autoantigens, i.e., La/SSB, and enzymes capable of proteolytically processing autoantigen, i.e., cathepsins B and D. A series of compartments identified as secretory vesicle membranes, prelysosomes, and microdomains of the trans-Golgi network involved in traffic to the basolateral membrane, to the secretory vesicles, and to the prelysosomes were all prominent loci of MHC class II molecules, La/SSB, and cathepsins B and D. These observations support the thesis that lacrimal gland acinar cells that have been induced to express MHC class II molecules function as autoantigen processing and presenting cells.
Yang
T
T
Department of Physiology, University of Southern California, Los Angeles, California 90033, USA.
Zeng
H
H
Zhang
J
J
Okamoto
C T
CT
Warren
D W
DW
Wood
R L
RL
Bachmann
M
M
Mircheff
A K
AK
D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001324:Autoantigens / Q000032:analysis*; D001692:Biological Transport / Q000276:immunology; D002401:Cathepsin B / Q000032:analysis*; D002402:Cathepsin D / Q000032:analysis*; D002458:Cell Fractionation / Q000379:methods; D002499:Centrifugation, Density Gradient / Q000379:methods; D004727:Endothelium / Q000737:chemistry / Q000201:enzymology / Q000276:immunology; D005260:Female; D005700:Galactosyltransferases / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D007765:Lacrimal Apparatus / Q000737:chemistry* / Q000201:enzymology* / Q000276:immunology; D008565:Membrane Proteins / Q000032:analysis; D011817:Rabbits; D012261:Ribonucleoproteins / Q000032:analysis*; D012859:Sjogren's Syndrome / Q000201:enzymology / Q000276:immunology; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D013347:Subcellular Fractions / Q000737:chemistry / Q000201:enzymology; D000520:alpha-Glucosidases / Q000032:analysis; D001619:beta-N-Acetylhexosaminidases / Q000032:analysis; D020691:rab GTP-Binding Proteins / Q000032:analysis; D000097585:SS-B Antigen
D000135:Acid Phosphatase; D001324:Autoantigens; D002401:Cathepsin B; D002402:Cathepsin D; D005700:Galactosyltransferases; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D012261:Ribonucleoproteins; D000254:Sodium-Potassium-Exchanging ATPase; D000520:alpha-Glucosidases; D001619:beta-N-Acetylhexosaminidases; D020691:rab GTP-Binding Proteins; D000097585:SS-B Antigen; C094135:Rab6 protein