Introduction of soluble proteins into the MHC class I pathway by conjugation to an HIV tat peptide

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.