Abstracts (complete list) - Wissenschaft Online

Chiara Massa, Christiane Kellert, Esther Kamphausen, Barbara Seliger
Disparate modulation of antigen processing components
during maturation of the different human DC subsets.
Dendritic cells (DC) are the most potent antigen presenting cells (APC) of the immune
system and have thus been employed in the cell-based approach to tumor
immunotherapy. After the modest successes obtained using DC pulsed with single
tumor-derived epitopes, the latest strategies aim at broadening the repertoire of
antigens provided by the vaccine in order to activate a more efficient immune response.
To this purpose DC vaccines have been loaded with the entire tumor antigenic
repertoire either in the form of RNA or proteins. In this therapeutic setting the final
pattern of epitopes presented to the immune system is shaped by the antigen
processing machinery of the DC and can thus be different from the one produced by the
tumor itself. Indeed, some tumor epitopes can be destroyed by the immunoproteasome
of professional APC. Aim of this study was to characterise the different subsets of
human DC for the constitutive expression of the cyosolic and reticular peptidases
involved in the antigen processing pathway and the modulation of these enzymes
during the maturation process. To this purpose, myeloid CD1c+ and plasmacytoid
BDCA4+DC were purified from the blood of healthy donors and stimulated with the
appropriate TLR ligand. CD14+ monocytes were differentiated into DC either using the
classical protocol of 7 days culture with GM-CSF and IL4 or the proposed amelioration
using IL15 for the generation of Langerhans-like cells or a shorter 2 days protocol. The
characterisation of the mRNA expression patterns of these enzymes revealed an
opposite behaviour among DC types: a prevalent down-regulation in the expression
pattern of peptidases was found in the plasmacytoid DC, whereas in myeloid DC the
enzymes are up-regulated, in particularly in response to poly IC. Functional experiments
will be performed to confirm whether the different expression patterns identified have
any consequences on the epitope repertoire presented by the DC types, thus providing
useful information for the establishment of DC-based vaccines that process tumor
antigens in the most tumor-like fashion.