8TQ8

Crystal structure of Fab.34.5.8 in complex with MHC-I (H2-Dd)

Summary for 8TQ8

• Entry DOI: 10.2210/pdb8tq8/pdb
• Related: 8TQ4 8TQ5 8TQ6 8TQ7 8TQ9 8TQA
• Descriptor: H-2 class I histocompatibility antigen, D-D alpha chain, Beta-2-microglobulin, Transmembrane protein gp41, ... (8 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: Mus musculus (house mouse); More
• Total number of polymer chains: 10
• Total formula weight: 184910.29

Authors

Jiang, J.,Boyd, L.F.,Natarajan, K.,Margulies, D.H. (deposition date: 2023-08-06, release date: 2024-03-20, Last modification date: 2024-10-16)

Primary citation

Boyd, L.F.,Jiang, J.,Ahmad, J.,Natarajan, K.,Margulies, D.H.
Experimental Structures of Antibody/MHC-I Complexes Reveal Details of Epitopes Overlooked by Computational Prediction.
J Immunol., 212:1366-1380, 2024

PubMed Abstract: mAbs to MHC class I (MHC-I) molecules have proved to be crucial reagents for tissue typing and fundamental studies of immune recognition. To augment our understanding of epitopic sites seen by a set of anti-MHC-I mAb, we determined X-ray crystal structures of four complexes of anti-MHC-I Fabs bound to peptide/MHC-I/β2-microglobulin (pMHC-I). An anti-H2-Dd mAb, two anti-MHC-I α3 domain mAbs, and an anti-β2-microglobulin mAb bind pMHC-I at sites consistent with earlier mutational and functional experiments, and the structures explain allelomorph specificity. Comparison of the experimentally determined structures with computationally derived models using AlphaFold Multimer showed that although predictions of the individual pMHC-I heterodimers were quite acceptable, the computational models failed to properly identify the docking sites of the mAb on pMHC-I. The experimental and predicted structures provide insight into strengths and weaknesses of purely computational approaches and suggest areas that merit additional attention.

PubMed: 38456672
DOI: 10.4049/jimmunol.2300839

Experimental method

X-RAY DIFFRACTION (2.69 Å)