Targeting dendritic cells for priming cellular immune responses

Péter Gogolák, Bence Réthi, György Hajas, Éva Rajnavölgyi

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The cardinal role of dendritic cells (DC) in priming adaptive immunity and in orchestrating immune responses against all classes of pathogens and also against tumors is well established. Their unique potential both to maintain self-tolerance and to initiate protective immune responses against foreign and/or dangerous structures is based on the functional diversity and flexibility of these cells. Tissue DC lining antigenic portals such as mucosal surfaces and the skin are specialized to take up a wide array of compounds including proteins, lipids, carbohydrates, glycoproteins, glycolipids and oligonucleotides, particles carrying such structures and apoptotic or necrotic cells. This process is facilitated by specialized receptors with high endocytic capacity, which provides potential targets for delivering designed molecules. The best route for targeting B- and/or T cell epitopes, however, is still the subject of intense investigation. Immature DC, which reside in various tissues, can be activated by pathogens, stress and inflammation or modified metabolic products, which induce mobilization of cells to draining lymph nodes where they act as highly potent professional antigen presenting cells. This is brought about by the ability to present their accumulated intracellular content for both CD4- helper (Th) and CD8- cytotoxic/cytolytic T lymphocytes (Tc/CTL). Engulfed proteins are processed intracellularly and their peptide fragments are transported to the cell surface in the context of major histocompatibility complex encoded class I and II molecules for presentation to Th cells and CTLs, respectively. The T cell priming capacity of DC, however, depends not only on antigen presentation but also on other features of DC. Human monocyte-derived DC provide an excellent tool to study the internalizing, antigen-presenting and T cell-activating functions of DC at their immature and activated differentiation states. These biological activities of DC, however, are highly dependent on their migratory potential from the peripheral non-lymphoid tissues to the lymph nodes, on the expression of adhesion molecules, which support the interaction of DC with T lymphocytes, and the cytokines secreted by DC, which polarize immune responses to ThI-mediated cellular or Th2-mediated antibody responses. These results altogether demonstrate that mono-cyte-derived DC are useful candidates for in vitro or in vivo targeting of antigens to induce efficient adaptive immune responses against pathogens and also against tumors.

Original languageEnglish
Pages (from-to)299-317
Number of pages19
JournalJournal of Molecular Recognition
Volume16
Issue number5
DOIs
Publication statusPublished - Sep 1 2003

Keywords

  • Antigen presentation
  • Cellular immune response
  • Dendritic cell
  • T lymphocyte
  • Targeting
  • Vaccination
  • Virus- and tumor-specific immunity

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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