Induction of a T cell mediated immune response is critical for the eradication of viral infections and tumours. Soluble peptide-loaded major histocompatibility complex-Ig ((pep-)MHC-Ig) have been shown to bind their cognate ligands, T cell receptor, with high affinity, and are successfully used to visualize antigen-specific T cells. Furthermore, immobilized (pep-)MHC-Ig can activate and expand antigen-specific T cells in vitro and in vivo. In this study, we investigate the use of (pep-)MHC-Ig as a potential strategy to modulate antigen specific T cell immune responses in vivo. (SIY-)K(b)-Ig immunization, together with the pre-activation by an anti-CD40 monoclonal antibody, is able to stimulate a strong expansio... More
Induction of a T cell mediated immune response is critical for the eradication of viral infections and tumours. Soluble peptide-loaded major histocompatibility complex-Ig ((pep-)MHC-Ig) have been shown to bind their cognate ligands, T cell receptor, with high affinity, and are successfully used to visualize antigen-specific T cells. Furthermore, immobilized (pep-)MHC-Ig can activate and expand antigen-specific T cells in vitro and in vivo. In this study, we investigate the use of (pep-)MHC-Ig as a potential strategy to modulate antigen specific T cell immune responses in vivo. (SIY-)K(b)-Ig immunization, together with the pre-activation by an anti-CD40 monoclonal antibody, is able to stimulate a strong expansion of adoptively transferred 2C transgenic T cells and the formation of long term antigen-specific memory T cells. In addition, mechanistic studies show that the (pep-)MHC-Ig molecules directly activate T cells in vivo without requiring uptake and reprocessing by antigen-presenting cells. Furthermore, B6 mice immunized with (pep-)MHC-Ig molecules inhibit tumour growth in a B16-SIY melanoma prevention model. Thus, soluble (pep-)MHC-Ig molecules represent a powerful tool for active immunotherapy.
