The roles of MHC class II, CD40, and B7 costimulation in CTL induction by plasmid DNA.
DNA-based vaccines generate potent CTL responses. The mechanism of T cell stimulation has been attributed to plasmid-transfected dendritic cells. These cells have also been shown to express plasmid-encoded proteins and to become activated by surface marker up-regulation. However, the increased surface expression of CD40 and B7 on these dendritic cells is insufficient to overcome the need for MHC class II-restricted CD4(+) T cell help in the priming of a CTL response. In this study, MHC class II(-/-) mice were unable to generate a CTL response following DNA immunization. This deficit in CTL stimulation by MHC class II-deficient mice was only modestly restored with CD40-activating Ab, suggesting that there were other elements provided by MHC class II-restricted T cell help for CTL induction. CTL activity was also augmented by coinjection with a vector encoding the costimulatory ligand B7.1, but not B7.2. These data indicate that dendritic cells in plasmid DNA-injected mice require conditioning signals from MHC class II-restricted T cells that are both CD40 dependent and independent and that there are different roles for costimulatory molecules that may be involved in inducing optimal CTL activity.
Chan
K
K
Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California at San Diego, La Jolla, CA 92093, USA.
Lee
D J
DJ
Schubert
A
A
Tang
C M
CM
Crain
B
B
Schoenberger
S P
SP
Corr
M
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000502:physiology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051940:B7-2 Antigen; D015704:CD4 Antigens / Q000235:genetics; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004269:DNA, Bacterial / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D004357:Drug Synergism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000502:physiology*; D007271:Injections, Intradermal; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015704:CD4 Antigens; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D004269:DNA, Bacterial; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D019444:Vaccines, DNA; D023201:CD40 Ligand