[1] Dendritic cells are central to the generation of adaptive immunity, continuously sampling their vicinity for antigens against which the body might need to react, such as from invading pathogenic microbes. Antigens are taken up by DC in soluble or particulate forms, often facilitated by opsonization by antibody or complement, processed by a series of enzymes and then loaded onto MHC molecules for presentation to T-cells during priming of an immune response.[2]

MHC class II usually presents antigenic peptides derived from extracellular organisms to CD4+ T-cells, whereas MHC class I presents peptides derived from intracellular organisms (or cytoplasmic proteins) to CD8+ T-cells. This ensures that the optimum T-cell response is generated: CD4+ T helper cells for antibodies and cell-mediated immunity against extracellular organisms, and CD8+ cytotoxic T-cells against intracellular organisms and U0126 cell line cancers. The DC also receive inflammatory signals during infections and cancers; pathogen-associated molecular patterns or danger signals, which are recognized via receptors such as Toll-like receptors and stimulate cytokine secretion and co-stimulatory molecule expression, which further facilitates T-cell responses.

Hence, various vaccination strategies aim to target DC because of their pivotal role in adaptive immunity. Delivering antigens to DC, using strategies that target uptake via 3-Methyladenine mouse surface receptors, including DEC-205, mannose receptor and FcγR1, is an innovative area for developing vaccines and therapeutics. Heat-shock proteins (hsp) carry an antigenic profile or fingerprint of the cells from which they are derived, possess adjuvant activity and bind to receptors on DC to promote uptake. This review highlights the role of hsp in antigen delivery

to DC, which forms the basis of a strategy for developing vaccines against cancer and infectious diseases. Within cells, hsp undertake critical and conserved physiological roles. They function as chaperones and co-chaperones binding intracellular polypeptide chains and misfolded proteins, preventing aggregation and supporting folding and transport.[3] Most hsp have at least two functional domains: a polypeptide-binding domain, and an ATPase domain controlling binding and release Ponatinib manufacturer of polypeptide substrate. Heat-shock proteins are present in organisms as diverse as bacteria and man, protecting proteins from damage during normal physiological activity as well as stressful conditions.[4] As a consequence of their physiological functions, hsp transport multiple proteins as ‘cargo’. Cellular levels of hsp are high, for example in bacteria, hsp70 alone accounts for 1–2% of cellular proteins after heat induction.[5] In eukaryotic cells hsp levels are increased by stressful stimuli including heat, oxidative stress, starvation, hypoxia, irradiation, viral infection and cancerous transformation.