Macrophages, lymphocytes, and dendritic cells (DCs) express a family of receptors, CR3, LFA-1, and p150,95, that function in adhesion reactions. CR3 mediates the binding of C3bi-coated particles, and LFA-1 mediates the binding of killer T cells to targets. We propose to examine the role of these and other receptors in the interaction between DCs and T cells. DCs bind T cells in an antigen-independent fashion, and such interaction appears to be a necessary prerequisite to T cell activation. We will remove individual receptors from the membranes of DC or T cells and observe their ability to interact. These studies will identify the complementary molecules on DC and T cells that mediate their interaction. We will also use immunoelectron microscopy to examine the cellular location of adhesion- promoting receptors. Preliminary studies suggest that CR3 can only initiate adhesion when present on the membrane in the distinct aggregates. We will observe the state of aggregation of aggregation of adhesion-promoting receptors in T cells that are competent and imcompetent to interact with DCs. Further, we will observe the location of adhesion-promoting receptors in clusters of DC and T cells to seek evidence that these receptors act to bridge interacting cells. Recent work indicates that CR3, LFA-1, and p150,95 can act as receptors for lipopolysaccharide (LPS). One of the earliest effects of LPS in MO is to """"""""prime"""""""" to cells such that they exhibit greatly enhanced capacity to release metabolites in response to several triggers. We will test the hypothesis that CR3, LFA-1, and p150,95 directly mediate the physiological responses to LPS. We will use antibodies against the CR3/LFA family of receptors to block the effect of LPS. We will also attempt to mimic the effect of LPS on MO by adding these antibodies. An early event in the priming of MO by LPS is the myristylation of several MO proteins. We will examine the capacity of antibodies against the CR3/LFA family to either block myristylation in response to LPS or to mimic the effect of LPS and induce myristylation. Finally, we will examine the role of the CR3/LFA family in AIDS. We will examine the expression and function of CR3/LFA family members in infected MO and in cells isolated from patients with AIDS.
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