Autoantibodies to the Golgi complex are found primarily in patients with Sj[unreadable]gren's syndrome and SLE although they are not restricted to these diseases. This competitive renewal application requests funding for the continuation of studies to characterize autoantigens of the Golgi complex and address the mechanisms that lead to the expression of autoantibodies to these intracellular organelle-associated proteins. The P.I.'s laboratory has been responsible for the identification of a family of Golgi antigens known as golgins. Common features of these autoantigens are that they are located on the cytoplasmic face of the Golgi cisternae and they have multiple alpha-helical coiled-coil rod domains flanked by non-coiled-coil and C- terminal domains. The goal of the proposed studies is to determine if the common structure and function for members of this protein family can explain the origin and production of autoantibodies in disease states. Specific Aim 1 will examine common features of golgins that may explain why they are targets of human anti-Golgi autoantibodies. The P.I. will characterize the events associated with the Golgi complex and golgins and their stability during apoptosis and necrosis. Hypotheses on how these autoantibodies may be produced in experimental models will be examined. Specific Aim 2 will examine if Golgi fragments and vesicular structures will induce immune and autoimmune response in experimental mice. Specific Aim 3 will elucidate the target of Golgi complex in lactate dehydrogenase-elevating virus (LDV) infected mice and address mechanism of how autoimmune response to the Golgi complex can be produced in these mice. Earlier studies have shown that LDV infected mice produce anti-Golgi antibodies. Our current data suggest that the autoimmune response to cytoplasmic organelles such as the Golgi complex is uniquely different from other intracellular autoantigens examined to date. It is anticipated that testing of the P.I.'s hypotheses will provide new insights into autoimmunity and autoimmune diseases associated with subcellular organelles.