9B7B
Crystal structure of humanized 44H10 Fab Version 22 in complex with HLA-DR (HLA-DRA*01:01/HLA-DRB1*04:01)
Summary for 9B7B
| Entry DOI | 10.2210/pdb9b7b/pdb |
| Descriptor | HLA class II histocompatibility antigen, DR alpha chain, Hemagglutinin HA1 chain, HLA class II histocompatibility antigen DR beta chain, h44H10-V22 Antibody, heavy chain, ... (6 entities in total) |
| Functional Keywords | antibody, humanized, mhc class ii, immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 8 |
| Total formula weight | 191261.77 |
| Authors | Kassardjian, A.,Julien, J.P. (deposition date: 2024-03-27, release date: 2024-08-07, Last modification date: 2024-10-30) |
| Primary citation | Kassardjian, A.,Ivanochko, D.,Barber, B.,Jetha, A.,Julien, J.P. Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework. Antibodies, 13:-, 2024 Cited by PubMed Abstract: Reducing the immunogenicity of animal-derived monoclonal antibodies (mAbs) for use in humans is critical to maximize therapeutic effectiveness and preclude potential adverse events. While traditional humanization methods have primarily focused on grafting antibody Complementarity-Determining Regions (CDRs) on homologous human antibody scaffolds, framework regions can also play essential roles in antigen binding. Here, we describe the humanization of the pan-HLA-DR mAb 44H10, a murine antibody displaying significant involvement of the framework region in antigen binding. Using a structure-guided approach, we identify and restore framework residues that directly interact with the antigen or indirectly modulate antigen binding by shaping the antibody paratope and engineer a humanized antibody with affinity, biophysical profile, and molecular binding basis comparable to that of the parental 44H10 mAb. As a humanized molecule, this antibody holds promise as a scaffold for the development of MHC class II-targeting therapeutics and vaccines. PubMed: 39051333DOI: 10.3390/antib13030057 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.08 Å) |
Structure validation
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