Targeting Antigens to Dendritic Cell Receptors for Vaccine Development

Dendritic cells (DCs) are highly specialized antigen presenting cells of the immune system which play a key role in regulating immune responses. Depending on the method of antigen delivery, DCs stimulate immune responses or induce tolerance. As a consequence of the dual function of DCs, DCs are studied in the context of immunotherapy for both cancer and autoimmune diseases. In vaccine development, a major aim is to induce strong, specific T-cell responses. This is achieved by targeting antigen to cell surface molecules on DCs that efficiently channel the antigen into endocytic compartments for loading onto MHC molecules and stimulation of T-cell responses. The most attractive cell surface receptors, expressed on DCs used as targets for antigen delivery for cancer and other diseases, are discussed. 1. Introduction The most successful vaccines used to combat infectious disease are the live or live attenuated organisms as used in polio and small pox vaccines. However, with purified proteins or peptides, in most cases adjuvants or suitable danger signals are necessary in order to prime T-cell responses. In the last decade, dendritic cells (DCs), powerful antigen presenting cells, have surfaced as the most important cells, to target antigens for uptake, processing, and presentation to T cells [1]. DCs link the innate immune response to the adaptive immune response in that they bind pathogens and are able to stimulate T-cell responses against antigens. Targeting antigens to DC is therefore an appropriate method to stimulate effective immune responses. Targeting cell surface receptors on DCs represents a more direct and less laborious method and has been the subject of considerable recent investigation. Numerous receptors have been identified to be expressed on DCs, including mannose receptor (MR), DC-SIGN, scavenger receptor (SR), DEC-205, and toll-like receptors. Targeting of these receptors is becoming an efficient strategy of delivering antigens in DC-based anticancer immunotherapy. Furthermore, pattern recognition receptors (PRRs) are expressed by cells of the innate immune system which bind to pathogen associated molecular patterns (PAMPs) on pathogens. PRRs are also known as pathogen recognition receptors or primitive pattern recognition receptors as they evolved before other parts of the immune system, mainly before adaptive immunity. PAMPs bind mannose, lipopolysaccharide, fucose, peptidoglycans, lipoproteins and glucans. PRRs are classified into 2 groups: (i) endocytic PRRs, which phagocytose microorganisms, bind to carbohydrates, and include the