Introduction of soluble proteins into the MHC class I pathway by conjugation to an HIV tat peptide
Kim, D.T.; Mitchell, D.J.; Brockstedt, D.G.; Fong, L.; Nolan, G.P.; Fathman, C.G.; Engleman, E.G.; Rothbard, J.B.
Journal of Immunology 159(4): 1666-1668
1997
ISSN/ISBN: 0022-1767 PMID: 9257826 Document Number: 475643
Protection against most intracellular pathogens requires T cells that recognize pathogen-derived peptides in association with major histocompatibility complex (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 cytotoxic T lymphocyte (CTL) responses have proved difficult to design. This problem was addressed by conjugating proteins, such as OVA, to a short cationic peptide derived from HIV-1 Tat (residues 49-57). When antigen-presenting cells 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, antigen-specific CTLs were generated in vivo by immunizing mice with histocompatible dendritic cells that had been exposed to protein-Tat conjugates.