SLP-76 and ADAP dependent dendritic cell function

Roswell Park Cancer Institute Corp, Buffalo NY

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Abstract

DESCRIPTION (provided by applicant): Dendritic cells have been the focus of intense investigation as potential adjuvants for the treatment of human disease due to the unique ability of these cells to elicit a potent antigen specific immune response. The past several years have witnessed a great deal of progress in the identification of multiple dendritic cell subsets based on differences in surface phenotype and function. However, very little is known regarding the biochemical signaling pathways that may contribute to the unique functional capacities of dendritic cells. In this study, we propose to identify those dendritic cell functions that are dependent on the adaptor proteins SLP-76 and ADAP. Our preliminary data confirm the expression of both SLP-76 and ADAP in murine bone marrow derived dendritic cells and indicate that these adaptors are not required for the in vitro generation of this cell type. Given the important role ascribed to SLP-76 and ADAP in regulating receptor dependent signaling events in several other hematopoietic cell types, it is hypothesized that these adaptors may also regulate key aspects of dendritic cell biology. To address this hypothesis, the ability of SLP-76 or ADAP deficient dendritic cells to stimulate an antigen specific T cell response will be assessed. The dependence of dendritic cell migration on SLP-76 and ADAP will also be determined. The results obtained from these studies will be used to guide a more detailed analysis of SLP-76 and ADAP mediated signaling in dendritic cells. It is anticipated that these studies will provide new insights regarding the biochemical mechanisms that contribute to unique aspects of dendritic cell function and may suggest strategies to enhance the therapeutic use of dendritic cells in the treatment of human disease.