Effector T cell stimulation using Staphylococcal enterotoxin G and I loaded HLA transgenic dendritic cells

Abstract

Abstract Staphylococcal enterotoxins (SE) induce powerful T cell stimulation with specificity for the variable beta (Vβ) region of the T cell receptor (TCR). Additionally, MHC in mice (H2) and humans (human leukocyte antigen; HLA) differ in binding superantigens and, in turn, provide different T cell activating potentials. We have previously demonstrated that SEG and SEI, administered together, elicited progression free survival of B16–F10 challenged HLA-DQ8 (DQ8; DQA1*0301 and DQB1*0302) transgenic mice. C57BL/6 (B6) mice did not benefit from SEG/SEI given post B16–F10 challenge, as expected, given a markedly reduced T cell proliferation in the B6 mice compared to the DQ8 mice. We provide evidence here of the potential of dendritic cells (DCs) to be the vector for a SEG and SEI immunotherapy. Primary antigen presenting cells, DCs and monocytes, were isolated from the bone marrow of DQ8 or HLA-DR3 (DRB1*0301) transgenic mice. SEG/SEI loaded DQ8 and DR3 DCs drove a strong B6 CD8 T cell response at low T cell:DC ratios; whereas both DQ8 and DR3 DCs at a high T cell:DC ratios activated CD4 T cells. Collectively, these data support incorporating SEG and SEI into the current DC based immunotherapeutic strategies to induce a stronger and direct anti-cancer T cell response.