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 liposomeswith incorporated MHC II/peptide complexes as a carrier system formultivalent antigen presentation to CD4 + T cells.Methods. Purified peptide pre-loaded MHC II molecules wereincorporated into small unilamellar liposomes and tested for their ability toactivate A2b T cells. The outcome of T cell activation by such liposomesin the absence of accessory cells was tested via flow cytometry and aT cell anergy assay.Results. Provided the presence of external co-stimulation,MHC II/peptide liposomes were able to induce proliferation of the A2b T cellclone. More importantly incubation of these T cells withMHC II/peptide liposomes in the absence of co-stimulation did not induceproliferation, however, a MHC/peptide ligand-density dependent downregulation of the TCR was observed. Interestingly, when T cells afterincubation with the MHC II/peptide liposomes were restimulated withtheir specific antigen in the presence of professional APC, these cellswere anergic.Conclusions. We propose MHC II/peptide liposomes as a novel meansto induce T cell anergy. The possibility to prepare tailor-madeliposomal formulations may provide liposomes with an important advantagefor applications in immunotherapy.