TY - JOUR
T1 - Mhc-ig induces memory t cell formation in vivo and inhibits tumour growth
AU - Schütz, Christian
AU - Zoso, Alessia
AU - Peng, Shiwen
AU - Bennett, Jonathon D.
AU - Schneck, Jonathan P.
AU - Oelke, Mathias
N1 - Publisher Copyright:
© 2014 The Authors.
PY - 2014/11
Y1 - 2014/11
N2 - 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, immobilizedpep MHC-Ig can activate and expand antigen-specific T cells in vitro and in vivo. In this study, we investigate the use ofpep MHC-Ig as a potential strategy to modulate antigen specific T cell immune responses in vivo.SIY Kb-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 thepep MHC-Ig molecules directly activate T cells in vivo without requiring uptake and reprocessing by antigen-presenting cells. Furthermore, B6 mice immunized withpep MHC-Ig molecules inhibit tumours growth in a B16-SIY melanoma prevention model. Thus, solublepep MHC-Ig molecules represent a powerful tool for active immunotherapy.
AB - 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, immobilizedpep MHC-Ig can activate and expand antigen-specific T cells in vitro and in vivo. In this study, we investigate the use ofpep MHC-Ig as a potential strategy to modulate antigen specific T cell immune responses in vivo.SIY Kb-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 thepep MHC-Ig molecules directly activate T cells in vivo without requiring uptake and reprocessing by antigen-presenting cells. Furthermore, B6 mice immunized withpep MHC-Ig molecules inhibit tumours growth in a B16-SIY melanoma prevention model. Thus, solublepep MHC-Ig molecules represent a powerful tool for active immunotherapy.
KW - Adoptive T cell transfer
KW - Cancer
KW - In vivo vaccination
KW - MHC-Ig
KW - Memory T cells
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UR - http://www.scopus.com/inward/citedby.url?scp=85051373884&partnerID=8YFLogxK
U2 - 10.1002/iid3.35
DO - 10.1002/iid3.35
M3 - Article
AN - SCOPUS:85051373884
VL - 2
SP - 181
EP - 192
JO - Immunity, inflammation and disease
JF - Immunity, inflammation and disease
SN - 2050-4527
IS - 3
ER -