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.
Kim
D T
DT
Department of Medicine, Stanford University School of Medicine, CA 94305, USA.
Mitchell
D J
DJ
Brockstedt
D G
DG
Fong
L
L
Nolan
G P
GP
Fathman
C G
CG
Engleman
E G
EG
Rothbard
J B
JB
D000818:Animals; D003713:Dendritic Cells / Q000502:physiology; D015696:Gene Products, tat / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D015395:Histocompatibility Antigens Class I; D054322:tat Gene Products, Human Immunodeficiency Virus; D010047:Ovalbumin