Heat shock proteins 70 and 60 share common receptors which are expressed on human monocyte‐derived but not epidermal dendritic cells

Priming of CTL by means of heat shock proteins (hsp) is dependent on antigen‐presenting cells (APC), which present the hsp‐associated peptides, via their cell surface MHC class I molecules, toCD8+ T cells. It has not yet been established how human (hu) hsp70 interacts with the major (hu)APC, the dendritic cells (DC). Here we show that (hu)hsp70 is specifically internalized intoCD14–, Toll‐like receptor 4– monocyte‐derived (hu)DC by receptor‐mediated endocytosis. We further demonstrate that (hu)hsp70 and (hu)hsp60 share the same receptors on (hu)monocyte‐derived DC. Both molecules as well as MHC class I molecules are spontaneously internalized and reach the MHC class II‐enriched compartments. Finally, freshly isolated (hu) epidermal Langerhans cells (LC), the DC of the skin, as well as CD34+‐derived LC do not bind hsp60 or hsp70. Given the likely importance of the internalization of hsp70 by APC in the induction of the immune responses, the finding that hsp60 and hsp70 are internalized through the same receptor(s) may explain why microbial hsp60 represents a major T cell antigen. This may rationalize the use of microbial hsp60 to primeimmune responses against microbes. The lack of hsp60/70 receptors on epidermal LC raises the crucial question as to whether absence of priming of the skin and mucosal immune systems by hsp‐polypeptide complexes could account for some tissue‐specific diseases. This work also points to a potential advantage of using monocyte‐derived DC in human immunotherapeutic applications of hsp60/70.

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