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MHC class II molecules, cathepsins, and La/SSB proteins in lacrimal acinar cell endomembranes

Departments of Physiology and Biophysics, Cell and Neurobiology, and Ophthalmology, School of Medicine, and Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90033; and Institut für Physiologische Chemie, Fachbereich Medzin, Johanne...

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Published in:American Journal of Physiology: Cell Physiology 1999-11, Vol.277 (5), p.C994-C1007
Main Authors: Yang, Tao, Zeng, Hongtao, Zhang, Jian, Okamoto, Curtis T, Warren, Dwight W, Wood, Richard L, Bachmann, Michael, Mircheff, Austin K
Format: Article
Language:English
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Summary:Departments of Physiology and Biophysics, Cell and Neurobiology, and Ophthalmology, School of Medicine, and Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90033; and Institut für Physiologische Chemie, Fachbereich Medzin, Johannes Gutenberg-Universität Mainz, Mainz, Germany 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. Sjögren's syndrome; autoantigen processing and presentation; membrane traffic
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.1999.277.5.C994