How does HSP70, affinity and Cbl-b influence autoimmunity?

Current models suggest that the maturation state of dendritic cells (DCs) determines whether T cell tolerance versus activation occurs. T cell receptor (TCR) specific interactions with peptide/MHC expressed by immature DCs leads to the induction of T cell tolerance, whereas TCR specific interactions with peptide/MHC on mature DCs leads to T cell activation. Although various signals between pathogen-derived molecules and Toll like receptors have been shown to promote DC maturation, the identification of endogenous molecules that can induce DC maturation and promote autoimmunity in vivo have remained elusive. We have examined the potential of mammalian HSP70 to promote autoimmunity in our experimental model of diabetes.

Because my labb is interested in the factors and mechanisms that lead to autoimmunity, we have developed a model to examine the role of affinity/avidity in the induction and progression of autoimmune disease. Our findings support an affinity/avidity model for autoimmune disease, with some surprising limitations and checkpoints in disease progression.