Idiotypic intramolecular help. Induction of tumor-specific antibodies by monoclonal anti-idiotypic antibody with the help of Fc-specific T helper clones.
In this study, the mechanism of anti-Id vaccination was investigated by using cloned Th cells and an anti-idiotypic mAb. 2F10, an anti-idiotypic mAb derived from an Igh1-e allotype mouse strain, which induces protection against the L1210/GZL DBA/2 tumor, was used to prime DBA/2 mice. An Fc (Igh1-e)-specific syngeneic Th clone was cocultured in the presence of 2F10 anti-Id with 2F10-Fab-primed B cells. The Th clone responded with proliferation and also provided help for 2F10-Fab-primed B cells to produce antibodies that bind to L1210/GZL and not to P815 tumor cells. Intact 2F10 anti-Id was presented to Fc-specific Th cells by Fab (or Id) primed B cells more efficiently than the fragment mixture (Fab plus Fc) of 2F10 anti-Id, indicating that 2F10-Fab (or Id)-primed B cells capture 2F10 anti-Id through surface Ig receptors. Presenting B cells are sensitive to treatment with chloroquine and must come from H-2 matched mice, indicating that the Ag presentation by Fab-primed B cells to Fc-specific Th cells requires processing and is MHC restricted. Collectively these results outline a mechanism that may operate in anti-Id therapy of tumor-bearing animals by using tumor Ag mimicking anti-idiotypic antibodies. A similar mechanism could be effective in tumor patients immunized with xenogeneic anti-idiotypic antibodies operating under the "intra(Ag) molecular help."
Saeki
Y
Y
Department of Pathology, University of California, San Diego, La Jolla 92093.
Chen
J J
JJ
Shi
L F
LF
Kohler
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000096:biosynthesis*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014612:Vaccines / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007141:Immunoglobulin Fc Fragments; D007130:Immunoglobulin Idiotypes; D014612:Vaccines