Heat shock proteins (HSPs) are important molecules required for ideal protein function. Extensive research on the functional properties of HSPs indicates that HSPs may be implicated in a wide range of physiological functions including immune function. In the immune system, HSPs are involved in cell proliferation, differentiation, cytokine release, and apoptosis. Therefore, the ability of the immune system, in particular immune cells, to function optimally and in unison with other physiological systems is in part dependent on signaling transduction processes, including bidirectional communication with HSPs. Regulatory T cells (Tregs) are important T cells with suppressive functions and impairments in their function have been associated with a number of autoimmune disorders. The purpose of this paper is to examine the relationship between HSPs and Tregs. The interrelationship between cells and proteins may be important in cellular functions necessary for cell survival and expansion during diseased state. 1. Introduction Optimal cellular function is regulated by several molecules including heat shock proteins (HSPs). These proteins have chaperone properties and are important in both stressed and unstressed cells. HSPs can be categorized into six diverse highly or less-conserved families. These include HSP10, HSP40, HSP60, HSP70, HSP90, and HSP100 [1–4]. HSP60 is found in the mitochondria [5]. HSP70 is implicated in protein transport assembly and synthesis. It has anti-apoptotic properties that are implicated in intrinsic and extrinsic apoptotic pathways. HSP70 interacts with the mitochondria through death receptor signaling where it binds to death receptors DR4 and DR5 impeding TNF-related apoptosis inducing ligand (TRAIL) [6]. Importantly, HSP70 can bind to either the unphosphorylated C terminus of protein kinase C or Akt prompting rephosphorylation and kinase stabilization [7]. ATP-dependent HSP90 regulates cell survival by stabilizing kinases such as Akt and suppressing apoptosis by inhibiting caspases [8, 9]. The exact structural domains for all human HSPs remains to be determined; however, HSP70 and HSP90 have been well characterized. HSP70 is comprised of an N-terminal nucleotide-binding domain with ATPase activity and a C terminal containing a substrate-binding domain [10–12]. HSP90 on the other hand has three characterized structural domains including an N-terminal nucleotide-binding domain, a middle segment and a C terminus [13–16]. Inter-domain interactions occur by a conserved linker [17]. HSPs are found in intracellular and extracellular spaces
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