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Induction of T Cell Anergy by Liposomes with Incorporated Major Histocompatibility Complex (MHC) II/Peptide Complexes

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Abstract

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-made’liposomal formulations may provide liposomes with an important advantagefor applications in immunotherapy.

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van Rensen, A.J.M.L., Taams, L.S., Grosfeld-Stulemeyer, M.C. et al. Induction of T Cell Anergy by Liposomes with Incorporated Major Histocompatibility Complex (MHC) II/Peptide Complexes. Pharm Res 17, 720–726 (2000). https://doi.org/10.1023/A:1007586400631

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  • DOI: https://doi.org/10.1023/A:1007586400631

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