T cell help is required to induce idiotypic–anti-idiotypic autoantibody network after immunization with complementary epitope 289–308aa of La/SSB autoantigen in non-autoimmune mice

Abstract

Summary Immunotherapies against autoimmune diseases have been of limited success. Preventive vaccines could be developed on the basis to abrogate unwanted immune responses to defined autodeterminants. In this study it is shown that immunization of BALB/c mice with two linear T and B cell epitopes of the human La/SSB autoantigen (spanning the regions 289–308aa and 349–364aa) and their complementary forms specified by the complementary mRNA, results in characteristic B and T cell responses. Mice immunized with the 289–308aa epitope or its complementary peptide elicited specific antibodies against both epitopes. In contrast, mice immunized with the 349–364aa epitope or its complementary peptide mounted antibody titres against the immunizing peptide only. According to these data, the 289–308aa epitope and its complementary form were capable to generate an idiotypic–anti-idiotypic response, which were cross-regulated. Peptide-specific T cell proliferation and cytokine production in vitro revealed the induction of a two-stage T helper response (Th1→Th2 type) after immunization with either the epitope 289–308 or its complementary peptide. IgG1 was the predominant subclass after immunization with the two forms of epitopes 289–308 and 349–364, while a response of the IgG2b > IgG2a was obtained after the immunization with the complementary form of 349–364 epitope reflecting the TH2/TH1 polarization, respectively. Our data suggest that the complementary peptides of two immunodominant epitopes of human LaSSB can mimic the autoantibodies against these epitopes and establish an active idiotypic–anti-idiotypic network.