SCAVENGER RECEPTOR FUNCTION IN CHAPERONE-ELICITED ADAPTIVE IMMUNE RESPONSES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our research program currently has two main foci: 1) the role of scavenger receptors in mediating leukocyte-driven adaptive immune responses, and 2) the role of leukocytes in ovarian cancer. The first project focuses on how scavenger receptors mediate the uptake of antigenic particles and how peptides derived from these particles then access the MHC class-I antigen presentation pathway and stimulate the hosts immune system. In pursuing this, we are now collaborating with a former COBRE junior investigator, Dr. Harry Higgs, to study how scavenger receptor class-A (SR-A) mediates the phagocytic uptake of bacteria and the endocytic uptake of molecular chaperones and their associated peptides. Our recent data has identified that SR-A is expressed by dendritic cells and contributes to the phagocytic uptake of bacteria by these cells (Amiel et al., Experimental Cell Research, 2007). Regarding chaperones, we are studying how chaperones function as adjuvants to enhance antigenic responses, using chaperone-stimulated dendritic cell maturation as an assay for identifying the underlying mechanisms. For the second project, we are collaborating with a current COBRE junior investigator, Dr. Jose Conejo-Garcia, to investigate scavenger receptors as a way to target tumor-infiltrating leukocytes and thereby therapeutically treat ovarian cancer. An anti-SR-A immunotoxin proved efficacious in depleting murine peritoneal ID8 ovarian tumor-recruited leukocytes and, importantly, leukocyte depletion blocked the ovarian tumor progression (Bak et al., Cancer Research, 2007). All of the above studies were supported by COBRE funding.