7T0L

HLA-B*27:05 in complex with the pan-HLA-Ia monoclonal antibody W6/32

Summary for 7T0L

• Entry DOI: 10.2210/pdb7t0l/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, PHE-ARG-TYR-ASN-GLY-LEU-ILE-HIS-ARG peptide, ... (5 entities in total)
• Functional Keywords: hla, antibody, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 182939.14

Authors

Vivian, J.P.,Rossjohn, J. (deposition date: 2021-11-29, release date: 2022-12-07, Last modification date: 2025-08-06)

Primary citation

Pymm, P.,Saunders, P.M.,Anand, S.,MacLachlan, B.J.,Faoro, C.,Hitchen, C.,Rossjohn, J.,Brooks, A.G.,Vivian, J.P.
The Structural Basis for Recognition of Human Leukocyte Antigen Class I Molecules by the Pan-HLA Antibody W6/32.
J Immunol., 213:876-885, 2024

PubMed Abstract: The central immunological role of HLA class I (HLA-I) in presenting peptide Ags to cellular components of the immune system has been the focus of intense study for >60 y. A confounding factor in the study of HLA-I has been the extreme polymorphism of these molecules. The mAb W6/32 has been a fundamental reagent bypassing the issue of polymorphism by recognizing an epitope that is conserved across diverse HLA-I allotypes. However, despite the widespread use of W6/32, the epitope of this Ab has not been definitively mapped. In this study, we present the crystal structure of the Fab fragment of W6/32 in complex with peptide-HLA-B*27:05. W6/32 bound to HLA-B*27:05 beneath the Ag-binding groove, recognizing a discontinuous epitope comprised of the α1, α2, and α3 domains of HLA-I and β2-microglobulin. The epitope comprises a region of low polymorphism reflecting the pan-HLA-I nature of the binding. Notably, the W6/32 epitope neither overlaps the HLA-I binding sites of either T cell Ag receptors or killer cell Ig-like receptors. However, it does coincide with the binding sites for leukocyte Ig-like receptors and CD8 coreceptors. Consistent with this, the use of W6/32 to block the interaction of NK cells with HLA-I only weakly impaired inhibition mediated by KIR3DL1, but impacted HLA-LILR recognition.

PubMed: 39093013
DOI: 10.4049/jimmunol.2400328

Experimental method

X-RAY DIFFRACTION (3 Å)