Heat shock proteins: friend and foe?
The heat shock proteins (Hsps) are families of proteins first described and later named due to their production by cells exposed to sudden elevations in temperature (Tissieres, Mitchell & Tracey, 1974). It is now apparent that Hsps are induced in all cells by many different environmental assaults including oxidative injury and infection with intracellular pathogens, and enable the cells to survive otherwise unfavourable conditions (Polla, 1988). Although cellular stress increases the synthesis of Hsps, many are also constitutively expressed and play an essential role in normal cell function. Hsps are classified into families according to molecular weight (Hsp90,70,60 and small Hsps) (Lindquist & Craig, 1986) and perform their functions by associating with, and functionally influencing, other proteins. For example, Hsp90 complexes with inactive steroid hormone receptors, probably performing a stabilizing function and preventing binding to DNA in the absence of hormone (Baulieu, 1987). Members of the Hsp70 and 60 families play roles in the folding and unfolding of proteins and in the assembly of oligomeric protein complexes (Cheng et al., 1989; Craig & Gross, 1991). These functions are anticipated to come to the fore during stressed conditions. The Hsp response is ubiquitous throughout the proand eukaryotic kingdoms, and Hsps are extraordinarily evolutionarily conserved molecules. The human homologue of the Hsp60 family, for example, has 40-50% sequence identity with the mycobacterial member, the 65-kDa antigen, and a further 20% conservative replacements (Jindal et al., 1989). For this reason Hsps would be predicted to be poorly immunogenic. Quite to the contrary, evidence suggests that Hsps may be some of the most important immunogens of infectious agents (see Verbon, Hartskeerl & Kolk, this issue). It has also been proposed that Hsps provide a link between immunity to infection and autoimmune disease. The evidence for, and anticipated consequences of, the immunogenicity of Hsps is discussed in this brief review.