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Induction of T cell anergy by liposomes with incorporated major histocompatibility complex (MHC) II/peptide complexes
A J van Rensen1, L S Taams, M C Grosfeld-Stulemeyer
1Department of Pharmaceutics, Faculty of Pharmacy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Purpose:
The aim of this study was to use small unilamellar liposomes with incorporated MHC II/peptide complexes as a carrier system for multivalent antigen presentation to CD4 + T cells.
Methods:
Purified peptide pre-loaded MHC II molecules were incorporated into small unilamellar liposomes and tested for their ability to activate A2b T cells. The outcome of T cell activation by such liposomes in the absence of accessory cells was tested via flow cytometry and a T cell anergy assay.
Results:
Provided the presence of external co-stimulation, MHC II/ peptide liposomes were able to induce proliferation of the A2b T cell clone. More importantly incubation of these T cells with MHC II/ peptide liposomes in the absence of co-stimulation did not induce proliferation, however, a MHC/peptide ligand-density dependent down-regulation of the TCR was observed. Interestingly, when T cells after incubation with the MHC II/peptide liposomes were restimulated with their specific antigen in the presence of professional APC, these cells were anergic.
Conclusions:
We propose MHC II/peptide liposomes as a novel means to induce T cell anergy. The possibility to prepare 'tailor-made' liposomal formulations may provide liposomes with an important advantage for applications in immunotherapy.