A new TLR2 agonist promotes cross-presentation by mouse and human antigen presenting cells

Hum Vaccin Immunother. 2015;11(8):2038-50. doi: 10.1080/21645515.2015.1027467.


Cross-presentation is the process by which professional APCs load peptides from an extracellularly derived protein onto class I MHC molecules to trigger a CD8(+) T cell response. The ability to enhance this process is therefore relevant for the development of antitumor and antiviral vaccines. We investigated a new TLR2-based adjuvant, Small Molecule Immune Potentiator (SMIP) 2.1, for its ability to stimulate cross-presentation. Using OVA as model antigen, we demonstrated that a SMIP2.1-adjuvanted vaccine formulation induced a greater CD8(+) T cell response, in terms of proliferation, cytokine production and cytolytic activity, than a non-adjuvanted vaccine. Moreover, using an OVA-expressing tumor model, we showed that the CTLs induced by the SMIP2.1 formulated vaccine inhibits tumor growth in vivo. Using a BCR transgenic mouse model we found that B cells could cross-present the OVA antigen when stimulated with SMIP2.1. We also used a flow cytometry assay to detect activation of human CD8(+) T cells isolated from human PBMCs of cytomegalovirus-seropositive donors. Stimulation with SMIP2.1 increased the capacity of human APCs, pulsed in vitro with the pp65 CMV protein, to activate CMV-specific CD8(+) T cells. Therefore, vaccination with an exogenous antigen formulated with SMIP2.1 is a successful strategy for the induction of a cytotoxic T cell response along with antibody production.

Keywords: APC, antigen presenting cell; B cells; BCR, B cell receptor; CMV, cytomegalovirus; CTL, cytotoxic t lymphocyte; DC, dendritic cell; HCMV, human CMV; KO, knock out; LN, lymph node; MHC, major histocompatibility complex; OVA, avalbumin; PBMC, peripheral blood mononuclear cell; SMIP, Small Molecule Immune Potentiator; TLR, toll like receptor; cross presentation/priming; cytotoxic T cells; dendritic cells; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / metabolism*
  • Animals
  • Antigen-Presenting Cells / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology
  • Cell Proliferation
  • Cross-Priming*
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Disease Models, Animal
  • Female
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasms, Experimental / therapy
  • Ovalbumin / immunology
  • Toll-Like Receptor 2 / agonists*


  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Cytokines
  • TLR2 protein, human
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Ovalbumin