Studies of the adjuvant-independent antibody response to immunotargeting. Target structure dependence, isotype distribution, and induction of long term memory.
Immunoconjugates composed of avidin linked to biotinylated antibodies specific for different surface determinants on cells of the immune system were evaluated for their ability to induce adjuvant-independent anti-avidin IgG responses in mice. Previously, we demonstrated that allele-specific murine anti-class II MHC-avidin immunoconjugates were immunogenic in mice bearing the appropriate haplotype. Herein we report the immunotargeting potential of heterologous anti-class II MHC antibodies specific for framework determinants, and extend the range of effective targets to include certain non-MHC structures present on APC (e.g., 33D1 on dendritic cells, 14.8 on B cells, and CD45--the leukocyte common antigen). However, antibodies with other specificities (e.g., leukocyte integrins and some macrophage markers) were not effective targeting vehicles. Surprisingly, immunoconjugates specific for CD3 and CD4 were immunogenic. The isotype distribution of the anti-avidin antibody response induced in mice by immunotargeting to class II MHC or 33D1 was similar to that induced by immunization with Ag emulsified in complete Freund's adjuvant. Most of the antibody induced was IgG1 (65-75%), but a significant proportion was IgG2a (20-30%). We also demonstrate that immunotargeting is able to prime for long-term immunologic memory in mice.
Department of Immunology, University of Toronto, Ontario, Canada.
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D001360:Avidin / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007132:Immunoglobulin Isotypes / Q000032:analysis*; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D001360:Avidin; D017493:Leukocyte Common Antigens