Diverse perturbations may alter the lacrimal acinar cell autoantigenic spectra.
Lacrimal gland acinar cell autoantigens in Sjögren's syndrome include both intracellular proteins and plasma membrane proteins, to which the immune system normally must be tolerant. Attention has largely focused on the roles apoptotic cell death may play in exposing sequestered autoantigens and novel surface epitopes. We hypothesize that perturbations of ongoing membrane traffic in intact, functioning cells may also increase autoantigen exposure. We review the vesicular traffic between acinar cell basal-lateral plasma membranes (blm) and endomembrane compartments, then describe experiments in which isolated acinar cells were stimulated with epidermal growth factor (EGF), lysed, and analyzed by sorbitol gradient centrifugation. Whereas the cholinergic agonist, carbachol, impairs traffic from the trans-Golgi network to prelysosomes, causing Golgi, secretory, and lysosomal proteins to reflux into domains of the trans-Golgi network that communicate with the blm and to accumulate in the blm, EGF specifically causes a 2.6-fold (P < 0.05) increase in the beta-hexosaminidase content of the blm fraction, apparently by impairing traffic from early endosomes to prelysosome. We, therefore, suggest that a variety of physiologic stimuli may alter the spectra of autoantigens acinar cells secrete to the interstitium, express in their blm, and present via MHC Class II molecules after proteolytic processing.
Mircheff
Austin K
AK
Department of Physiology & Biophysics, and Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. amirchef@hsc.usc.edu
Xie
Jiansong
J
Qian
Limin
L
Hamm-Alvarez
Sarah F
SF
D000818:Animals; D001324:Autoantigens / Q000096:biosynthesis / Q000737:chemistry*; D001485:Basement Membrane / Q000276:immunology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000276:immunology*; D011817:Rabbits; D012859:Sjogren's Syndrome / Q000276:immunology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D001324:Autoantigens; D004815:Epidermal Growth Factor; D002217:Carbachol; D001619:beta-N-Acetylhexosaminidases