Introduction

Heat shock or stress proteins are important intracellular protein chaperones that control their trafficking. The function of heat shock proteins in the immunopathology of infections, tumours and autoimmune diseases has been the subject of numerous experimental and clinical investigations over the past few decades and some of their properties are summarised in Table 10.1. Because there is extensive homology between mammalian and microbial heat shock proteins, immunological cross-reactions were considered to account for a number of autoimmune diseases. However, although the biological significance of lipopolysaccharide (LPS) found in Gram-negative bacteria has been well appreciated, heat shock proteins, which are found more widely in Gram-negative and -positive bacteria, especially those in the gut, have received more limited attention. A relatively new phase in this area of biology was initiated by the discovery of specific heat shock protein receptors and by rapid advances in our understanding of the signalling pathways. This chapter will deal with the receptors used by heat shock proteins, with particular reference to Hsp70, involvement of these proteins in the stimulation of chemokine production, maturation of dendritic cells (DCs), their intrinsic adjuvanticity and capacity to enhance immunogenicity.

Structural features of Hsp70

Although the overall three-dimensional structure of Hsp70 is not known, the structures of the two domains from various members of the family have been solved separately. The crystal structures of the ATPase domains of bovine Hsc70 (heat shock constitutive protein) and human Hsp70 have been determined [1, 2].