title: Breaking B-cell tolerance and CTL tolerance in three OVA-transgenic mouse strains expressing different levels of OVA.
abstract: It is of major importance to overcome the immunological tolerance in attempts to generate efficient tumour vaccines. Here, we describe induction of autoantibodies and self-reactive CTL in three types of OVA-transgenic mouse strains, RIP-OVA(low), RIP-mOVA and RIP-OVA(HI) exhibiting varying levels of OVA expression and tolerance. This was achieved by immunizing with DNA constructs where a foreign T-helper epitope, P30 from tetanus toxin, was inserted into the OVA sequence. OVA wild-type DNA as well as the P30-modified OVA DNA vaccines (OVA-P30) were constructed and used for immunization in the OVA-transgenic mouse strains as well as in control C57Bl/6 mice. The data show that insertion of a foreign T-helper peptide (P30) in OVA is sufficient for breaking B-cell tolerance in three different OVA-transgenic mice strain. This approach is sufficient for induction of self-reactive CTL in two of the three strains that expressed either a membrane-bound form of OVA or a low amount of soluble OVA. It was not possible to induce CTL but still possible to induce autoantibodies in the strain that expressed a higher level of soluble OVA.
authors.affiliation: Pharmexa A/S, Kogle Allé 6, Hørsholm, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Steinaa
authors.forename: P B
authors.initials: PB
authors.lastname: Rasmussen
authors.forename: A
authors.initials: A
authors.lastname: Gautam
authors.forename: S
authors.initials: S
authors.lastname: Mouritsen
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D049109:Cell Proliferation; D004247:DNA / Q000737:chemistry / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D013744:Tetanus Toxin / Q000737:chemistry / Q000235:genetics; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D013744:Tetanus Toxin; D019444:Vaccines, DNA; D010047:Ovalbumin; D004247:DNA