International Immunology, Vol 10, 1299-1304, Copyright © 1998 by Oxford University Press
MC Agnes, A Tan, R Jordens, A Geluk, BO Roep, T Ottenhoff, JW Drijfhout and F Koning
Altered peptide ligands (APL) have the potential to modulate pathogenic T
cell reactivity. High concentrations of APL, however, are required to
achieve efficient blocking of the T cell response. We have therefore
investigated whether improved delivery of APL to professional antigen-
presenting cells (APC) can lead to more efficient application of such
peptides. For this purpose APL were bis-mannosylated in order to facilitate
their uptake by mannose receptor-positive dendritic cells (DC) in vitro. We
present evidence that a 100- to 1000-fold lower concentration of
bis-mannosylated APL was sufficient for complete blocking of the
proliferative T cell response against the agonist peptide compared to the
non-mannosylated APL. Moreover, bis- mannosylated APL were similarly
effective in the inhibition of the T cell response against whole protein
antigens. In contrast, unrelated, bis-mannosylated class II binding
peptides were ineffective, indicating that the increased efficiency of the
mannosylated APL was not due to competition for binding to class II
molecules. Furthermore, a strong increase in the efficiency of presentation
of APL was also observed when macrophages and peripheral blood mononuclear
cells were used as APC. Thus, bis-mannosylation of APL greatly increases
their potency to inhibit proliferative T cell responses. Moreover, it is
likely that the use of bis-mannosylated APL will result in preferential
presentation by mannose receptor-positive, professional APC. These results
may be of relevance for more effective use of APL for immunoregulation in
vivo.
ARTICLES
Strongly increased efficiency of altered peptide ligands by mannosylation
Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands.
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