Human anti‐idiotypic antibodies can be good immunogens as they target FC receptors on antigen‐presenting cells allowing efficient stimulation of both helper and cytotoxic T‐cell responses

Anti‐idiotypic antibodies that mimic tumour‐associated antigens can stimulate anti‐tumour T‐cell responses. In this article, we have studied the role of Fc in the presentation of T‐cell epitopes by 2 anti‐idiotypic antibodies, 105AD7 and 708. The human monoclonal antibody 105AD7, which mimics CD55, stimulated strong in vitro T‐cell proliferation, γIFN secretion and redirected cytotoxicity in unprimed T cells from healthy donors. However, removal of the Fc region of the anti‐idiotype reduced the sensitivity of the assay 1,000‐fold, as did inhibiting Fc uptake of the anti‐idiotype by an excess of human IgG. The mouse anti‐idiotype 708, which mimics CEA, failed to stimulate in vitro T‐cell responses on unprimed T cells from healthy donors. However, when a human IgG1 Fc region replaced its mouse Fc region, the anti‐idiotype induced T‐cell proliferation, γIFN secretion and redirected cytotoxicity in lymphocytes from unimmunised donors. Human anti‐idiotypes are therefore good immunogens since they target Fc receptors on antigen‐presenting cells, allowing efficient stimulation of both helper and cytotoxic T‐cell responses. The immunogenicity of other anti‐idiotypes may therefore be enhanced by human Fc targeting of antigen‐presenting cells. © 2001 Wiley‐Liss, Inc.