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, gammaIFN 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, gammaIFN 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.
Durrant
L G
LG
CRC Academic Unit of Clinical Oncology, University of Nottingham, City Hospital, Nottingham, United Kingdom. lindy.durrant@nottingham.ac.uk
Parsons
T
T
Moss
R
R
Spendlove
I
I
Carter
G
G
Carr
F
F
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D051379:Mice; D011961:Receptors, Fc / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014612:Vaccines / Q000276:immunology
C405618:105AD7 antibody; D000888:Antibodies, Anti-Idiotypic; D011961:Receptors, Fc; D014612:Vaccines