Strongly increased efficiency of altered peptide ligands by mannosylation

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...

Full description

Saved in:
Bibliographic Details
Published in:International immunology 1998-09, Vol.10 (9), p.1299-1304
Main Authors: Agnes, M C, Tan, A, Jordens, R, Geluk, A, Roep, B O, Ottenhoff, T, Drijfhout, J W, Koning, F
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - chemical synthesis
Adjuvants, Immunologic - pharmacology
Amino Acid Sequence
Antigen-Presenting Cells - drug effects
Antigen-Presenting Cells - immunology
HLA-DR Antigens - immunology
Humans
Ligands
Lymphocyte Activation - drug effects
Mannose - analogs & derivatives
Mannose - metabolism
Mannose - pharmacology
Molecular Sequence Data
Oligopeptides - chemical synthesis
Oligopeptides - immunology
Oligopeptides - pharmacology
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0953-8178
1460-2377
1460-2377
DOI:10.1093/intimm/10.9.1299