3HPJ

Human Class I MHC HLA-A2 in complex with the WT-1 (126-134) peptide

Summary for 3HPJ

• Entry DOI: 10.2210/pdb3hpj/pdb
• Related: 1TVB 3MYJ
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, WT126 peptide, ... (5 entities in total)
• Functional Keywords: wt-1, wt1, wt126 peptide, nonapeptide, mhc class i, hla-a2, cancer vaccine, disulfide bond, glycoprotein, host-virus interaction, immune response, membrane, mhc i, phosphoprotein, transmembrane, disease mutation, glycation, immunoglobulin domain, pyrrolidone carboxylic acid, secreted, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted . Note=(Microbial infection) In the presence of M: P61769; Nucleus . Isoform 1: Nucleus speckle . Isoform 4: Nucleus, nucleoplasm : P19544
• Total number of polymer chains: 6
• Total formula weight: 90146.23

Authors

Borbulevych, O.Y.,Baker, B.M. (deposition date: 2009-06-04, release date: 2010-06-23, Last modification date: 2024-11-06)

Primary citation

Borbulevych, O.Y.,Do, P.,Baker, B.M.
Structures of native and affinity-enhanced WT1 epitopes bound to HLA-A*0201: Implications for WT1-based cancer therapeutics.
Mol.Immunol., 47:2519-2524, 2010

PubMed Abstract: Presentation of peptides by class I or class II major histocompatibility complex (MHC) molecules is required for the initiation and propagation of a T cell-mediated immune response. Peptides from the Wilms Tumor 1 transcription factor (WT1), upregulated in many hematopoetic and solid tumors, can be recognized by T cells and numerous efforts are underway to engineer WT1-based cancer vaccines. Here we determined the structures of the class I MHC molecule HLA-A*0201 bound to the native 126-134 epitope of the WT1 peptide and a recently described variant (R1Y) with improved MHC binding. The R1Y variant, a potential vaccine candidate, alters the positions of MHC charged side chains near the peptide N-terminus and significantly reduces the peptide/MHC electrostatic surface potential. These alterations indicate that the R1Y variant is an imperfect mimic of the native WT1 peptide, and suggest caution in its use as a therapeutic vaccine. Stability measurements revealed how the R1Y substitution enhances MHC binding affinity, and together with the structures suggest a strategy for engineering WT1 variants with improved MHC binding that retain the structural features of the native peptide/MHC complex.

PubMed: 20619457
DOI: 10.1016/j.molimm.2010.06.005

Experimental method

X-RAY DIFFRACTION (2 Å)