Abstract
Abstract CD91 is an endocytic receptor on Antigen Presenting Cells for the immunogenic Heat Shock Proteins (HSPs) gp96, hsp70, hsp90 and calreticulin. Binding of HSPs to CD91 initiates immune responses through cross presentation of the HSP-chaperoned peptides and elaboration of co-stimulatory signals. In vitro, various CD91 ligands compete with HSPs for receptor binding; the serum protein alpha-2-macroglobulin (a2M) is one such ligand. In light of this observation, we hypothesize that modulation of a2M levels in animals will affect the immunogenicity of HSP-vaccines. Elevated levels of a2M are achieved by initiating an acute inflammatory response and monitored by ELISA. Immune responses following HSP vaccination are measured by in vivo CTL assays. The results from these experiments will impact on-going and future clinical trials in cancer patients vaccinated with HSP-peptide complexes.
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