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 mo lecules on the surface of infected cells, However, because exogenous p roteins do not ordinarily enter the cytosol and access the MHC class I -processing pathway, protein-based vaccines that induce class I-restri cted 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 expose d in vitro to such protein conjugates, they processed and presented th e peptides in association with MHC class I molecules and stimulated CD 8(+) 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-fat conjugates.