title: CD4+ T cell epitope affinity to MHC II influences the magnitude of CTL responses elicited by DNA epitope vaccines.
abstract: Immunization with naked plasmid DNA elicits strong cell-mediated immune responses. In the present study, we examine strategies to enhance epitope-specific cytotoxic T lymphocyte (CTL) responses using DNA constructs, expressing a minimal class I epitope of the gp120 of HIV-IIIB. Here, we evaluate the effect of CD4+ T cell (T(H)) epitope affinity for the MHC II molecule on the immunogenicity of our DNA vaccines. Our data indicate that a low-affinity T(H) epitope decreased the magnitude of the CTL responses. In addition, we observed decreased numbers of epitope-specific T helper cells and CTLs, as well as diminished cytokine secretion and proliferative responses. Thus, the immunogenicity of a DNA epitope vaccine can be modulated by altering the affinity of the T(H) epitope.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA. dvatakis@ucla.edu
authors.forename: Dimitrios N
authors.initials: DN
authors.lastname: Vatakis
authors.forename: Yi Ting
authors.initials: YT
authors.lastname: Koh
authors.forename: Minnie
authors.initials: M
authors.lastname: McMillan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002860:Chromium Radioisotopes; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005802:Genes, MHC Class II / Q000276:immunology*; D005822:Genetic Vectors; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D002860:Chromium Radioisotopes; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA; D013936:Thymidine