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The Journal of Immunology, 2003, 170: 194-200.
Copyright © 2003 by The American Association of Immunologists

Toll-Like Receptor 2 Ligands as Adjuvants for Human Th1 Responses1

Peter A. Sieling2,*, Woosin Chung*, Baochau T. Duong*, Paul J. Godowski§ and Robert L. Modlin*,{dagger},{ddagger}

* Division of Dermatology, {dagger} Department of Microbiology and Immunology, and {ddagger} Molecular Biology Institute, David Gefffen School of Medicine, University of California, Los Angeles, CA 90095; and § Genentech Incorporated, South San Francisco, CA 94080

Bacterial lipopeptides (bLPs) are increasingly used as adjuvants to activate cell-mediated immune responses to foreign Ags. To explore mechanisms whereby bLPs adjuvant T cell responses, we stimulated human PBMCs with bLPs. We found that bLPs stimulate T cells to proliferate and produce IFN-{gamma} in an accessory cell-dependent manner and in the absence of exogenous protein Ags. The ability of bLPs to stimulate T cell proliferation was Toll-like receptor 2 dependent and required IL-12, interaction with costimulatory molecules, and MHC proteins. Our data suggest that bLPs adjuvant adaptive Th1 responses by enhancing Ag presentation of endogenous peptides.




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