Keyhole limpet hemocyanin induces the activation and maturation of human dendritic cells through the involvement of mannose receptor

Keyhole limpet hemocyanin (KLH) is a xenoantigen largely used in vitro as an immunogen to study primary antigen-specific T cell responses and in vivo as a vaccine component with optimal carrier qualities. So far, the mechanisms by which KLH exerts its immunostimulatory properties are still largely unknown. In particular, although dendritic cells (DCs) play a central role in the initiation and activation of immune responses, the effects of KLH on these cells have been poorly explored. In the present study we investigated the effects of KLH on DCs differentiated in vitro from human monocytes. We observed that KLH promotes the activation and maturation of DCs, as assessed by up-regulation of the surface expression of CD80, CD86, CD40, HLA-DR and CD83. Moreover, even if KLH stimulated the production of IL-12 and IL-10 by DCs, the final balance was clearly in favour of IL-12. According to these stimulatory effects, KLH significantly increased the allostimulatory activity of DCs. To verify whether these effects of KLH may be related to the binding of this highly glycosilated molecule to mannose receptor (MR), we performed inhibition experiments with anti-MR antibody. Results showed that the stimulatory activity of KLH is indeed partially mediated by its interaction with MR. Taken together, our results seem to indicate that KLH does promote the maturation of DCs endowed with the ability to stimulate cell-mediated immune responses. We suggest that this property of KLH may represent a novel further mechanism by which this molecule may exert its efficacy when co-administered with others antigens in immunotherapeutic protocols.