7ZFR

Crystal structure of HLA-DP (DPA1*02:01-DPB1*01:01) in complex with a peptide bound in the reverse direction

Summary for 7ZFR

• Entry DOI: 10.2210/pdb7zfr/pdb
• Related: 7ZAK
• Descriptor: MHC class II HLA-DP alpha chain (DPA1*02:01), MHC class II HLA-DP beta chain (DPB1*01:01), Synthetic peptide, ... (4 entities in total)
• Functional Keywords: hla class ii, human leukocyte antigen class ii, mhc class ii, major histocompatibility complex class ii, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 61440.16

Authors

Racle, J.,Guillaume, P.,Larabi, A.,Lau, K.,Pojer, F.,Gfeller, D. (deposition date: 2022-04-01, release date: 2023-04-12, Last modification date: 2024-10-23)

Primary citation

Racle, J.,Guillaume, P.,Schmidt, J.,Michaux, J.,Larabi, A.,Lau, K.,Perez, M.A.S.,Croce, G.,Genolet, R.,Coukos, G.,Zoete, V.,Pojer, F.,Bassani-Sternberg, M.,Harari, A.,Gfeller, D.
Machine learning predictions of MHC-II specificities reveal alternative binding mode of class II epitopes.
Immunity, 56:1359-1375.e13, 2023

PubMed Abstract: CD4 T cells orchestrate the adaptive immune response against pathogens and cancer by recognizing epitopes presented on class II major histocompatibility complex (MHC-II) molecules. The high polymorphism of MHC-II genes represents an important hurdle toward accurate prediction and identification of CD4 T cell epitopes. Here we collected and curated a dataset of 627,013 unique MHC-II ligands identified by mass spectrometry. This enabled us to precisely determine the binding motifs of 88 MHC-II alleles across humans, mice, cattle, and chickens. Analysis of these binding specificities combined with X-ray crystallography refined our understanding of the molecular determinants of MHC-II motifs and revealed a widespread reverse-binding mode in HLA-DP ligands. We then developed a machine-learning framework to accurately predict binding specificities and ligands of any MHC-II allele. This tool improves and expands predictions of CD4 T cell epitopes and enables us to discover viral and bacterial epitopes following the aforementioned reverse-binding mode.

PubMed: 37023751
DOI: 10.1016/j.immuni.2023.03.009

Experimental method

X-RAY DIFFRACTION (2.9 Å)