It has been recently reported a methodology of manipulating antibody and T cell-mediated autoimmune responses via activation of anti-idiotypic and/or anti-clonotypic networks. This methodology was based on immunization with the complementary peptide against antigen receptors on epitope-specific B and T cells. The region 289-308 of the La/SSB protein is one of the four linear B cell epitopes which is recognized by sera from patients with primary Sjogren's Syndrome (pSS) and by different predictive methods share also putative T cell epitope properties. The 289-308 epitope (denoted Po25) and its complemetary form encoded by complementary RNA (denoted Pcpl25) were conjugated on Sequential Oligopeptide Carrier (SOCn). SOCn is formed by the (Lys-Aib-Gly)n sequential motif, where n = 2-7, and the peptide antigens were anchored to the lysine groups so as they retain their original structure and they obtain favorable molecular recognition conformations. Different doses of peptide carrier formulations were administrated alone or together with Freud's adjuvant (CFA/IFC) and specific antibody and lymphoproliferative response were determined. Both the in vivo and in vitro responses were dose dependent and a demonstrable cross reactivity was observed at the T and the B cell level. Immunization with Po25-SOC resulted to the induction of anti-Pcpl25-antibodies and immunization with Pcpl25 led to the production of anti-Po25 response indicating the regulatory activity of anti-idiotypic antibodies. On the other hand immunized mice also primed specific T cell proliferative responses in spleen. The ability of complementary peptides to prime both anti-idiotypic and T lymhocyte responses may be central to their potent immunization properties in regulating autoreactive B and T cells. With this approach we aim to shed light to the immunoregulatory mechanism(s) which underline the autoimmune response.