title: Affinity and epitope profiling of mouse anti-CD40 monoclonal antibodies.
abstract: The CD40-CD40L interaction plays a critical role in both humoral and cellular immune responses and interfering antibodies have been suggested as an effective approach for the treatment of lymphomas and autoimmune diseases. In this study we have profiled a panel of mouse antihuman CD40 monoclonal antibodies (MoAbs), regarding their CD40 binding affinity and epitope-specificity relative to the CD40L binding in relation to their cellular activating potential. Despite a rather similar domain-recognition profile, the MoAbs blocked the CD40L binding to a varying degree, with MoAb 5C3 being the poorest inhibitor. There was no correlation between affinity and cellular activation potential. In contrast, a correlation between the ability to block CD40L-binding and activation potential could be seen. We believe that this analysis of several mouse anti-CD40 antibodies can be used to develop strategies for producing new human anti-CD40 antibodies that can more effectively induce or block B-cell proliferation.
authors.affiliation: Department of Immunotechnology, Lund University, Lund, Sweden.
authors.forename: A-C
authors.initials: AC
authors.lastname: Malmborg Hager
authors.forename: P
authors.initials: P
authors.lastname: Ellmark
authors.forename: C A K
authors.initials: CA
authors.lastname: Borrebaeck
authors.forename: C
authors.initials: C
authors.lastname: Furebring
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D019013:CD40 Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D018604:Epitope Mapping; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D011994:Recombinant Proteins; D023201:CD40 Ligand