title: MHC-Ig induces memory T cell formation in vivo and inhibits tumour growth.
abstract: 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.
authors.affiliation: Department of Pathology, The Johns Hopkins Institute of Cell Engineering Baltimore, Maryland, 21205.
authors.forename: Christian
authors.initials: C
authors.lastname: Schütz
authors.affiliation: Diabetes Research Institute, University of Miami Miami, Florida, 33136.
authors.forename: Alessia
authors.initials: A
authors.lastname: Zoso
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions Baltimore, Maryland, 21205.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Peng
authors.affiliation: National Institutes of Health, National Institute on Aging, Biomedical Research Center Baltimore, Maryland, 21224.
authors.forename: Jonathon D
authors.initials: JD
authors.lastname: Bennett
authors.affiliation: Department of Pathology, The Johns Hopkins Institute of Cell Engineering Baltimore, Maryland, 21205.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Schneck
authors.affiliation: Department of Pathology, The Johns Hopkins Institute of Cell Engineering Baltimore, Maryland, 21205.
authors.forename: Mathias
authors.initials: M
authors.lastname: Oelke
keywords: Adoptive T cell transfer; MHC-Ig; cancer; in vivo vaccination; memory T cells