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The Journal of Immunology, Vol 159, Issue 4 1666-1668, Copyright © 1997 by American Association of Immunologists
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DT Kim, DJ Mitchell, DG Brockstedt, L Fong, GP Nolan, CG Fathman, EG Engleman and JB Rothbard
Department of Medicine, Stanford University School of Medicine, CA 94305, USA.
Protection against most intracellular pathogens requires T cells that recognize pathogen-derived peptides in association with MHC class I molecules on the surface of infected cells. However, because exogenous proteins do not ordinarily enter the cytosol and access the MHC class I- processing pathway, protein-based vaccines that induce class I- restricted CTL responses have proved difficult to design. We have addressed this problem by conjugating proteins, such as OVA, to a short cationic peptide derived from HIV-1 tat (residues 49-57). When APC were exposed in vitro to such protein conjugates, they processed and presented the peptides in association with MHC class I molecules and stimulated CD8+ Ag-specific T cells. Moreover, Ag-specific CTLs were generated in vivo by immunizing mice with histocompatible dendritic cells that had been exposed to protein-tat conjugates.
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