Targeting of hepatitis C virus core protein for MHC I or MHC II presentation does not enhance induction of immune responses to DNA vaccination.

作者: O. Vidalin , E. Tanaka , U. Spengler , C. Trepo , G. Inchauspe

DOI: 10.1089/104454999315024

关键词:

摘要: We analyzed different vaccine approaches aimed at enhancing CD4+- and CD8+-dependent responses against hepatitis C virus (HCV) core antigen. Specific DNA vectors expressing various forms of the in fusion with ubiquitin or lysosome-associated membrane protein (LAMP) were generated. These expressed full-length wildtype core; as a covalent ubiquitin; noncovalent containing N-stabilizing N-destabilizing residue; LAMP sequence. In vitro expression levels plasmids differed by much tenfold. After injection into mice, none yielded detectable antibody response, whereas core-specific cytotoxic T-lymphocyte (CTL) activity could be observed all long 21 weeks postimmunization. No increase CTL (ranging from 7% to 34% specific lysis) was ubiqu...

参考文章(57)
F.G. Guarnieri, L.M. Arterburn, M.B. Penno, Y. Cha, J.T. August, The motif Tyr-X-X-hydrophobic residue mediates lysosomal membrane targeting of lysosome-associated membrane protein 1 Journal of Biological Chemistry. ,vol. 268, pp. 1941- 1946 ,(1993) , 10.1016/S0021-9258(18)53945-4
Nilabh Shastri, Samuel Goth, Vu Nguyen, GENERATION OF NATURALLY PROCESSED PEPTIDE/MHC CLASS I COMPLEXES IS INDEPENDENT OF THE STABILITY OF ENDOGENOUSLY SYNTHESIZED PRECURSORS Journal of Immunology. ,vol. 157, pp. 1894- 1904 ,(1996)
M Shirai, H Okada, M Nishioka, T Akatsuka, C Wychowski, R Houghten, C D Pendleton, S M Feinstone, J A Berzofsky, An epitope in hepatitis C virus core region recognized by cytotoxic T cells in mice and humans. Journal of Virology. ,vol. 68, pp. 3334- 3342 ,(1994) , 10.1128/JVI.68.5.3334-3342.1994
R P Ricciardi, W U Gerhard, C J Hackett, L C Eisenlohr, J Yewdell, K B Eager, J Bennink, Murine cell lines stably expressing the influenza virus hemagglutinin gene introduced by a recombinant retrovirus vector are constitutive targets for MHC class I- and class II-restricted T lymphocytes. Journal of Immunology. ,vol. 143, pp. 2328- 2335 ,(1989)
D J Ecker, J M Stadel, T R Butt, J A Marsh, B P Monia, D A Powers, J A Gorman, P E Clark, F Warren, A Shatzman, S T Crooker, Increasing gene expression in yeast by fusion to ubiquitin Journal of Biological Chemistry. ,vol. 264, pp. 7715- 7719 ,(1989) , 10.1016/S0021-9258(18)83293-8
R F Siliciano, P E Stanhope, J F Rowell, Endocytosis of endogenously synthesized HIV-1 envelope protein. Mechanism and role in processing for association with class II MHC. Journal of Immunology. ,vol. 155, pp. 473- 488 ,(1995)
Robert F. Siliciano, Timothy Tobery, Cutting Edge: Induction of Enhanced CTL-Dependent Protective Immunity In Vivo by N-End Rule Targeting of a Model Tumor Antigen Journal of Immunology. ,vol. 162, pp. 639- 642 ,(1999)
Young S. Hahn, Young S. Hahn, Mary Kathryn Large, David J. Kittlesen, Suppression of Host Immune Response by the Core Protein of Hepatitis C Virus: Possible Implications for Hepatitis C Virus Persistence Journal of Immunology. ,vol. 162, pp. 931- 938 ,(1999)