The proposed research will describe the murine complement receptor Cr2. This gene produces two related proteins whose primary functions have been described as receptors for opsonized fragments of complement. During a viral or bacterial infection, the complement pathway is engaged to both lyse the invading pathogen as well as to coat the surface with protein subunits derived primarily from the C3 product. These bound protein fragments can then be recognized by a variety of different receptor chains to internalize and hopefully neutralize the pathogen. This pathway, however, can be exploited by pathogens such as HIV which can essentially hijack the complement pathway to gain entry into cells for which they lack the appropriate receptor. We plan to focus upon two related aspects of the gene and gene products. First is to describe those genetic control sequences which promote the expression of Cr2 in murine B cells and follicular dendritic cells and inhibit its expression in virtually all other cell types. This question will be approached by creating a variety of genetic constructs and analyzing them using both in vitro and in vivo techniques. The second phase of the research is to determine the role of the Cr2 proteins in the acquisition of an immune response to invading pathogens. These experiments will focus upon the role of the Cr2 chains to promote the uptake of antigen by B cells and the role of the protein on the follicular dendritic cell. The biological information we obtain from these studies should just as amenable to understanding the function(s) of human CR2 as the murine protein.
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