Induction of T cell anergy by liposomes with incorporated major histocompatibility complex (MHC) II/peptide complexes

Purpose. The aim of this study was to use small unilamellar liposomes with incorporated MHC II/peptide complexes as a carrier system for multivalent a ntigen presentation to CD4 + T cells. Methods. Purified peptide pre-loaded MHC II molecules were incorporated int o 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 l iposomes were able to induce proliferation of the A2b T cell clone. More im portantly incubation of these T cells with MHC II/peptide liposomes in the absence of co-stimulation did not induce proliferation, however, a MHC/pept ide ligand-density dependent downregulation of the TCR was observed. Intere stingly, when T cells after incubation with the MHC II/peptide liposomes we re 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 formulat ions may provide liposomes with an important advantage for applications in immunotherapy.