4IHO

Crystal structure of H-2Db Y159F in complex with chimeric gp100

Summary for 4IHO

• Entry DOI: 10.2210/pdb4iho/pdb
• Related: 3CCH 3CH1
• Descriptor: H-2 class I histocompatibility antigen, D-B alpha chain, Beta-2-microglobulin, NONAMERIC PEPTIDE CHIMERIC GP100, ... (6 entities in total)
• Functional Keywords: mhc, h-2db, glycoprotein, immune response, mhc i, transmembrane, immunoglobulin domain, disease mutation, melanoma, immune system, tumor associated antigen, altered peptide ligand, t cell receptor
• Biological source: Mus musculus (mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01899; Secreted: P01887
• Total number of polymer chains: 6
• Total formula weight: 90154.82

Authors

Uchtenhagen, H.,Stahl, E.,Achour, A. (deposition date: 2012-12-19, release date: 2013-09-11, Last modification date: 2024-11-13)

Primary citation

Uchtenhagen, H.,Abualrous, E.T.,Stahl, E.,Allerbring, E.B.,Sluijter, M.,Zacharias, M.,Sandalova, T.,van Hall, T.,Springer, S.,Nygren, P.A.,Achour, A.
Proline substitution independently enhances H-2D(b) complex stabilization and TCR recognition of melanoma-associated peptides
Eur.J.Immunol., 43:3051-3060, 2013

PubMed Abstract: The immunogenicity of H-2D(b) (D(b)) restricted epitopes can be significantly increased by substituting peptide position 3 to a proline (p3P). The p3P modification enhances MHC stability without altering the conformation of the modified epitope allowing for T-cell cross-reactivity with the native peptide. The present study reveals how specific interactions between p3P and the highly conserved MHC heavy chain residue Y159 increase the stability of D(b) in complex with an optimized version of the melanoma-associated epitope gp10025-33 . Furthermore, the p3P modification directly increased the affinity of the D(b)/gp10025-33 -specific T-cell receptor (TCR) pMel. Surprisingly, the enhanced TCR binding was independent from the observed increased stability of the optimized D(b)/gp10025-33 complex and from the interactions formed between p3P and Y159, indicating a direct effect of the p3P modification on TCR recognition.

PubMed: 23939911
DOI: 10.1002/eji.201343456

Experimental method

X-RAY DIFFRACTION (2.8 Å)