The objective of this application is to assess whether or not autoimmune disease in MRL mice is the result of T cell recognition of aberrant (non H-2) kappa MHC antigens which are expressed during active disease. 1.
Aim : (NEW) Subpopulations of lymphoid and non-lymphoid cells derived from MRL/1pr or MRL/++ mice of different ages will be evaluated using an extensive panel of monoclonal antibodies to Class I and Class II antigens. Any subsets of cells which specifically stain with non H-2 kappa antibodies will be sorted and reanalyzed by FACS. They will additionally be evaluated by functional analyses in vitro, and by 2D gel electrophoresis. 2.
Aim : (REVISED) Heterogeneous T cells, panned or sorted L3T4+ and Ly2+ cells derived from different aged MRL mice will be evaluated for their auto and alloreactivity in vitro using a panel of stimulator cells. 3.
Aim : (REVISED) Heterogeneous T cells, panned or sorted L3T4+ cells and T cell clones from different aged MRL mice will be evaluated for their autoreactivity to vascular smooth muscle cells derived from MRL mice with vasculitis. 4.
Aim (REVISED) Cell lines and clones will be recovered from MuLV-M infected MRL mice. Their phenotype and genotype will be determined and the capacity to activate MRL T cells in vitro will be explored. 5.
Aim : (NEW) The basis of T cell anergy in MRL mice will be addressed. Macrophages from MRL/1pr or MRL/++ with autoimmune disease will be cocultured with T cells and T cell subsets, and the (possible) induction of suppression in the L3T4+ T cell subset evaluated. Methodology: Fluorescence Activated Cell Sorter Analysis and Sorting, mixed lymphocyte cultures, chromium release assays, pepsin digestion of monoclonal antibodies, the culture of vascular smooth muscle cells, panning of T cell subpopulations, retrovirus- infection of MRL/1pr and MRL/++ mice; cloning of retrovirus- infected cells.
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