MOLECULAR MECHANISMS OF LYMPHOCYTE INTERACTIONS IN SLE

Yale University, New Haven CT

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Abstract

DESCRIPTION (Adapted from investigator's Abstract): The presence of anti-snRNP autoantibodies are often found in SLE patients. In these patients, antibodies to multiple components of this complex are detected. During the current grant period, the role of B cells in the origination of this immune response in mice in the context of molecular mimicry has been examined and preliminary data have been obtained indicating that accessory molecules which are involved in T-B cognate interactions may be important in the generation of an autoimmune response. This proposal is to extend the current work to examine how autoimmunity to the snRNP complex is originated and to identify important intercellular interactions that occur during the evolution of SLE. Four specific aims are proposed: 1) to generate anti-snRNP immunoglobulin mice and to examine antigen processing of the snRNP by antigen specific APCs; 2) to study the ability of antigen specific APCs to prime autoreactive T cells and to determine how these T cells drive the spectrum of anti-snRNP autoantibody response; 3) to determine the role of accessory molecules in the anti-snRNP autoimmunity in normal and autoimmune prone MRL lpr/lpr and MRL +/+; and 4) to examine the interactions of autoimmune prone (MRL-derived) B and T cells with the repertoire of lymphocytes in non-autoimmune mice.