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A set of rat-human and rat-rat chimeric mAb has been created, all possessing V regions identical in their specificity for the mouse CD8 Ag. In vitro all antibodies were able to block cell-mediated lysis but varied greatly in their capacity to utilize rabbit complement. We examined the ability of these chimeric antibodies to deplete in vivo and established a clear hierarchy. Of the human IgG subclasses, only IgG1, 2, and 3 could fix complement in vitro, yet all (IgG1-4) were remarkably potent at depleting CD8+ PBL in vivo. In contrast, human IgA2 and IgE were ineffective at clearing CD8+ PBL. The vector system used to create these antibodies together with the small doses of antibodies required to deplete in vivo make this a simple and rapid system for testing the effects of different antibody isotypes and mutants. We have shown that a mutant of human IgG1, which is incapable of fixing complement, depletes perfectly well in vivo, whereas an aglycosyl IgG1 mutant is rendered inactive. Our model provides a unique opportunity to study effector functions and motifs that are used by mAb in vivo and will help in the design of improved antibodies for human therapy.

Type

Journal article

Journal

J Immunol

Publication Date

15/05/1992

Volume

148

Pages

3062 - 3071

Keywords

Animals, Antibodies, Monoclonal, Base Sequence, CD8 Antigens, Complement System Proteins, Humans, Immunoglobulin G, Immunoglobulin Isotypes, Mice, Mice, Inbred CBA, Models, Biological, Molecular Sequence Data, Rats, Recombinant Fusion Proteins, T-Lymphocytes, Cytotoxic