| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Medicine/Oncology and
Pediatrics, Stanford University Medical Center, Stanford, CA 94305
This study was designed to test whether cytotoxic T cell (CTL) responses to DNA vaccination are dependent upon MHC class II-restricted priming of CD4+ T cells. Because DNA vaccination may directly transfect dendritic cells, and dendritic cells may be capable of directly stimulating CD8+ T cell responses, such priming might be unnecessary. To test this hypothesis, C57BL/6 mice were immunized intramuscularly or intradermally with DNA encoding either whole OVA, a class I (Kb)-restricted peptide epitope of OVA (amino acids 257–264, SIINFEKL), or this class I-restricted epitope plus the adjacent class II (I-Ab)-restricted epitope of OVA (amino acids 265–280, TEWTSSNVMEERKIKV). Very low to negligible CTL responses were observed in mice vaccinated with the SIINFEKL construct, whereas mice vaccinated with the SIINFEKLTEWTSSNVMEERKIKV or with the complete OVA construct made equally robust CTL responses. These responses were sensitive to blocking by anti-CD8 mAb and were shown to be SIINFEKL-specific by using SIINFEKL peptide-pulsed EL-4 cells as targets. To ensure that the generation of these CTL responses was indeed dependent upon CD4+ T cell help, mice were depleted of either CD4+ or CD8+ cells before immunization. Depletion of CD4+ cells completely abrogated the CTL response to OVA DNA, as did depletion of CD8+ cells. Thus, we conclude that the CTL response to both intramuscular and intradermal DNA vaccination is highly dependent upon the generation of CD4+ T cell help via a class II MHC-dependent pathway. These results will be relevant for the construction of minimal-epitope vaccines for DNA immunization.
This article has been cited by other articles:
|
|
 |
|
  M. S. Bijker, S. J. F. van den Eeden, K. L. Franken, C. J. M. Melief, R. Offringa, and S. H. van der Burg CD8+ CTL Priming by Exact Peptide Epitopes in Incomplete Freund's Adjuvant Induces a Vanishing CTL Response, whereas Long Peptides Induce Sustained CTL Reactivity J. Immunol., October 15, 2007; 179(8): 5033 - 5040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Bins, M. C. Wolkers, M. D. van den Boom, J. B. A. G. Haanen, and T. N. M. Schumacher In Vivo Antigen Stability Affects DNA Vaccine Immunogenicity J. Immunol., August 15, 2007; 179(4): 2126 - 2133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Applequist, E. Rollman, M. D. Wareing, M. Liden, B. Rozell, J. Hinkula, and H.-G. Ljunggren Activation of Innate Immunity, Inflammation, and Potentiation of DNA Vaccination through Mammalian Expression of the TLR5 Agonist Flagellin J. Immunol., September 15, 2005; 175(6): 3882 - 3891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Takamura, K. Matsuo, Y. Takebe, and Y. Yasutomi Ag85B of Mycobacteria Elicits Effective CTL Responses through Activation of Robust Th1 Immunity as a Novel Adjuvant in DNA Vaccine J. Immunol., August 15, 2005; 175(4): 2541 - 2547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Fraser, S. R. Leib, B. S. Zhang, R. H. Mealey, W. C. Brown, and T. C. McGuire Lymphocyte Proliferation Responses Induced to Broadly Reactive Th Peptides Did Not Protect against Equine Infectious Anemia Virus Challenge Clin. Vaccine Immunol., August 1, 2005; 12(8): 983 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Steinaa, P. B. Rasmussen, A. M. Wegener, L. Sonderbye, D. R. Leach, J. Rygaard, S. Mouritsen, and A. M. Gautam Linked Foreign T-Cell Help Activates Self-Reactive CTL and Inhibits Tumor Growth J. Immunol., July 1, 2005; 175(1): 329 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kennedy, A. H. Undale, W. C. Kieper, M. S. Block, L. R. Pease, and E. Celis Direct Cross-Priming by Th Lymphocytes Generates Memory Cytotoxic T Cell Responses J. Immunol., April 1, 2005; 174(7): 3967 - 3977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Okada, T. Tsugawa, H. Sato, N. Kuwashima, A. Gambotto, K. Okada, J. E. Dusak, W. K. Fellows-Mayle, G. D. Papworth, S. C. Watkins, et al. Delivery of Interferon-{alpha} Transfected Dendritic Cells into Central Nervous System Tumors Enhances the Antitumor Efficacy of Peripheral Peptide-Based Vaccines Cancer Res., August 15, 2004; 64(16): 5830 - 5838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Teramoto, K. Kontani, Y. Ozaki, S. Sawai, N. Tezuka, T. Nagata, S. Fujino, Y. Itoh, O. Taguchi, Y. Koide, et al. Deoxyribonucleic Acid (DNA) Encoding a Pan-Major Histocompatibility Complex Class II Peptide Analogue Augmented Antigen-specific Cellular Immunity and Suppressive Effects on Tumor Growth Elicited by DNA Vaccine Immunotherapy Cancer Res., November 15, 2003; 63(22): 7920 - 7925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kariyone, T. Tamura, H. Kano, Y. Iwakura, K. Takeda, S. Akira, and K. Takatsu Immunogenicity of Peptide-25 of Ag85B in Th1 development: role of IFN-{gamma} Int. Immunol., October 1, 2003; 15(10): 1183 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Dayball, J. Millar, M. Miller, Y. H. Wan, and J. Bramson Electroporation Enables Plasmid Vaccines to Elicit CD8+ T Cell Responses in the Absence of CD4+ T Cells J. Immunol., October 1, 2003; 171(7): 3379 - 3384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. T. A. Marques Jr., P. Chikhlikar, L. B. de Arruda, I. C. Leao, Y. Lu, J. Wong, J.-S. Chen, B. Byrne, and J. T. August HIV-1 p55Gag Encoded in the Lysosome-associated Membrane Protein-1 as a DNA Plasmid Vaccine Chimera Is Highly Expressed, Traffics to the Major Histocompatibility Class II Compartment, and Elicits Enhanced Immune Responses J. Biol. Chem., September 26, 2003; 278(39): 37926 - 37936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hashimoto, H.-S. Chen, C. Cunningham, T. H. Malik, and P. K. Lai Two Major Histocompatibility Complex Class I-Restricted Epitopes of the Borna Disease Virus p10 Protein Identified by Cytotoxic T Lymphocytes Induced by DNA-Based Immunization J. Virol., May 15, 2003; 77(10): 6076 - 6081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lobell, R. Weissert, S. Eltayeb, K. L. de Graaf, J. Wefer, M. K. Storch, H. Lassmann, H. Wigzell, and T. Olsson Suppressive DNA Vaccination in Myelin Oligodendrocyte Glycoprotein Peptide-Induced Experimental Autoimmune Encephalomyelitis Involves a T1-Biased Immune Response J. Immunol., February 15, 2003; 170(4): 1806 - 1813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rice, S. Buchan, and F. K. Stevenson Critical Components of a DNA Fusion Vaccine Able to Induce Protective Cytotoxic T Cells Against a Single Epitope of a Tumor Antigen J. Immunol., October 1, 2002; 169(7): 3908 - 3913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Campos-Neto, J. R. Webb, K. Greeson, R. N. Coler, Y. A. W. Skeiky, and S. G. Reed Vaccination with Plasmid DNA Encoding TSA/LmSTI1 Leishmanial Fusion Proteins Confers Protection against Leishmania major Infection in Susceptible BALB/c Mice Infect. Immun., June 1, 2002; 70(6): 2828 - 2836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Wolkers, M. Toebes, M. Okabe, J. B. A. G. Haanen, and T. N. M. Schumacher Optimizing the Efficacy of Epitope-Directed DNA Vaccination J. Immunol., May 15, 2002; 168(10): 4998 - 5004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Marzo, V. Vezys, K. Williams, D. F. Tough, and L. Lefrancois Tissue-Level Regulation of Th1 and Th2 Primary and Memory CD4 T Cells in Response to Listeria Infection J. Immunol., May 1, 2002; 168(9): 4504 - 4510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Alfonso, J.-O. Han, G. S. Williams, and L. Karlsson The Impact of H2-DM on Humoral Immune Responses J. Immunol., December 1, 2001; 167(11): 6348 - 6355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Cho, J. W. Youn, and Y. C. Sung Cross-Priming as a Predominant Mechanism for Inducing CD8+ T Cell Responses in Gene Gun DNA Immunization J. Immunol., November 15, 2001; 167(10): 5549 - 5557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Rodriguez, S. Harkins, J. M. Redwine, J. M. de Pereda, and J. L. Whitton CD4+ T Cells Induced by a DNA Vaccine: Immunological Consequences of Epitope-Specific Lysosomal Targeting J. Virol., November 1, 2001; 75(21): 10421 - 10430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Parajuli, V. Pisarev, J. Sublet, A. Steffel, M. Varney, R. Singh, D. LaFace, and J. E. Talmadge Immunization with Wild-Type p53 Gene Sequences Coadministered with Flt3 Ligand Induces an Antigen-specific Type 1 T-Cell Response Cancer Res., November 1, 2001; 61(22): 8227 - 8234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Fujimura, S. S. Kinoshita, V. L. Pereira-Chioccola, and M. M. Rodrigues DNA Sequences Encoding CD4+ and CD8+ T-Cell Epitopes Are Important for Efficient Protective Immunity Induced by DNA Vaccination with a Trypanosoma cruzi Gene Infect. Immun., September 1, 2001; 69(9): 5477 - 5486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Wang, C. C. Norbury, R. Greenwood, J. R. Bennink, J. W. Yewdell, and J. A. Frelinger Multiple Paths for Activation of Naive CD8+ T Cells: CD4-Independent Help J. Immunol., August 1, 2001; 167(3): 1283 - 1289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rice, T. Elliott, S. Buchan, and F. K. Stevenson DNA Fusion Vaccine Designed to Induce Cytotoxic T Cell Responses Against Defined Peptide Motifs: Implications for Cancer Vaccines J. Immunol., August 1, 2001; 167(3): 1558 - 1565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Kumar, J. Maglione, J. Thatte, B. Pederson, E. Sercarz, and E. S. Ward Induction of a type 1 regulatory CD4 T cell response following V{beta}8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis Int. Immunol., June 1, 2001; 13(6): 835 - 841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Chan, D. J. Lee, A. Schubert, C. M. Tang, B. Crain, S. P. Schoenberger, and M. Corr The Roles of MHC Class II, CD40, and B7 Costimulation in CTL Induction by Plasmid DNA J. Immunol., March 1, 2001; 166(5): 3061 - 3066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Kumaraguru, I. A. Davis, S. Deshpande, S. S. Tevethia, and B. T. Rouse Lymphotoxin {{alpha}}-/- Mice Develop Functionally Impaired CD8+ T Cell Responses and Fail to Contain Virus Infection of the Central Nervous System J. Immunol., January 15, 2001; 166(2): 1066 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Krishnan, S. Sad, G. B. Patel, and G. D. Sprott Archaeosomes Induce Long-Term CD8+ Cytotoxic T Cell Response to Entrapped Soluble Protein by the Exogenous Cytosolic Pathway, in the Absence of CD4+ T Cell Help J. Immunol., November 1, 2000; 165(9): 5177 - 5185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Cochlovius, M. Stassar, O. Christ, L. Raddrizzani, J. Hammer, I. Mytilineos, and M. Zoller In Vitro and In Vivo Induction of a Th Cell Response Toward Peptides of the Melanoma-Associated Glycoprotein 100 Protein Selected by the TEPITOPE Program J. Immunol., October 15, 2000; 165(8): 4731 - 4741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. DONNELLY, M. A. LIU, and J. B. ULMER Antigen Presentation and DNA Vaccines Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): S190 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Simmons, P. Mastroeni, R. Fowler, M. Ghaem-maghami, N. Lycke, M. Pizza, R. Rappuoli, and G. Dougan MHC Class I-Restricted Cytotoxic Lymphocyte Responses Induced by Enterotoxin-Based Mucosal Adjuvants J. Immunol., December 15, 1999; 163(12): 6502 - 6510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Corr, A. von Damm, D. J. Lee, and H. Tighe In Vivo Priming by DNA Injection Occurs Predominantly by Antigen Transfer J. Immunol., November 1, 1999; 163(9): 4721 - 4727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Tsitoura, R. H. DeKruyff, J. R. Lamb, and D. T. Umetsu Intranasal Exposure to Protein Antigen Induces Immunological Tolerance Mediated by Functionally Disabled CD4+ T Cells J. Immunol., September 1, 1999; 163(5): 2592 - 2600. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
