8TQ6
Crystal structure of Fab.B1.23.2 in complex with MHC-I (HLA-B*44:05)
Summary for 8TQ6
| Entry DOI | 10.2210/pdb8tq6/pdb |
| Related | 8TQ4 8TQ5 8TQ7 8TQ8 8TQ9 8TQA 9D73 9D74 9OA9 |
| Descriptor | HLA class I histocompatibility antigen B alpha chain (HLA-B*44:05), Beta-2-microglobulin, MHC class II antigen peptide, ... (5 entities in total) |
| Functional Keywords | histocompatibility complex class i, mhc-i, immune response, immune system fab, antibody, anti-mhc antibody, cancer tumor, immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 10 |
| Total formula weight | 182302.38 |
| Authors | Jiang, J.,Natarajan, K.,Boyd, L.F.,Margulies, D.H. (deposition date: 2023-08-06, release date: 2025-02-05, Last modification date: 2026-02-11) |
| Primary citation | Jiang, J.,Panda, A.K.,Natarajan, K.,Lei, H.,Sharma, S.,Boyd, L.F.,Towler, R.R.,Chempati, S.,Ahmad, J.,Morton, A.J.,Lang, Z.C.,Sun, Y.,Sgourakis, N.,Meier-Schellersheim, M.,Huang, R.K.,Shevach, E.M.,Margulies, D.H. Structural mechanism of anti-MHC-I antibody blocking of inhibitory NK cell receptors in tumor immunity. Commun Biol, 2026 Cited by PubMed Abstract: Anti-major histocompatibility complex class I (MHC-I) mAbs can stimulate immune responses to tumors and infections by blocking suppressive signals delivered via various immune inhibitory receptors. To understand such functions, we determined the structure of a highly cross-reactive anti-human MHC-I mAb, B1.23.2, in complex with the MHC-I molecule HLA-B*44:05 by both cryo-electron microscopy (cryo-EM) and X-ray crystallography. Structural models determined by the two methods were essentially identical revealing that B1.23.2 binds a conserved region on the α2 helix that overlaps the killer immunoglobulin-like receptor (KIR) binding site. Structural comparison to KIR/HLA complexes reveals a mechanism by which B1.23.2 blocks inhibitory receptor interactions, leading to natural killer (NK) cell activation. B1.23.2 treatment of the human KLM-1 pancreatic cancer model in humanized (NSG-IL15) mice provides evidence of suppression of tumor growth. Such anti-MHC-I mAb that block inhibitory KIR/HLA interactions may prove useful for tumor immunotherapy. PubMed: 41629525DOI: 10.1038/s42003-026-09641-8 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.2 Å) |
Structure validation
Download full validation report
