Preprint Journal Article Epublish
PubMed: 38106040 DOI: 10.1101/2023.12.01.569627
Experimental structures of antibody/MHC-I complexes reveal details of epitopes overlooked by computational prediction.
bioRxiv
Authors: Lisa F Boyd, Jiansheng Jiang, Javeed Ahmad, Kannan Natarajan, David H Margulies
Affiliations
- Molecular Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD, 20892-1892.
Abstract
Monoclonal antibodies (mAb) to major histocompatibility complex 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 antigen-binding fragments (Fab) bound to peptide/MHC-I/β 2m (pMHC-I). An anti-H2-D d mAb, two anti-MHC-I α3 domain mAb, and an anti-β 2-microglobulin (β 2m) 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 (AF-M) 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.
MeSH
Epitopes, Major Histocompatibility Complex, Histocompatibility Antigens Class I