4H1L

TCR interaction with peptide mimics of nickel offers structural insights in nickel contact allergy

Summary for 4H1L

• Entry DOI: 10.2210/pdb4h1l/pdb
• Related: 4H25 4H26
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, MHC class II antigen, mimotope peptide, ... (5 entities in total)
• Functional Keywords: protein-protein complex, immunoglobin fold, tcr recogniton of mhc, mhc ii, glycosidation, membrane, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P01903
• Total number of polymer chains: 10
• Total formula weight: 138353.32

Authors

Kappler, J.W.,Yin, L.,Dai, S.,Marrack, P. (deposition date: 2012-09-10, release date: 2012-11-14, Last modification date: 2013-09-04)

Primary citation

Yin, L.,Crawford, F.,Marrack, P.,Kappler, J.W.,Dai, S.
T-cell receptor (TCR) interaction with peptides that mimic nickel offers insight into nickel contact allergy.
Proc.Natl.Acad.Sci.USA, 109:18517-18522, 2012

PubMed Abstract: T cell-mediated allergy to Ni(++) is one of the most common forms of allergic contact dermatitis, but how the T-cell receptor (TCR) recognizes Ni(++) is unknown. We studied a TCR from an allergic patient that recognizes Ni(++) bound to the MHCII molecule DR52c containing an unknown self-peptide. We identified mimotope peptides that can replace both the self-peptide and Ni(++) in this ligand. They share a p7 lysine whose εNH(2) group is surface-exposed when bound to DR52c. Whereas the TCR uses germ-line complementary-determining region (CDR)1/2 amino acids to dock in the conventional diagonal mode on the mimotope-DR52c complex, the interface is dominated by the TCR Vβ CDR3 interaction with the p7 lysine. Mutations in the TCR CDR loops have similar effects on the T-cell response to either the mimotope or Ni(++) ligand. We suggest that the mimotope p7 lysine mimics Ni(++) in the natural TCR ligand and that MHCII β-chain flexibility in the area around the peptide p7 position forms a common site for cation binding in metal allergies.

PubMed: 23091041
DOI: 10.1073/pnas.1215928109

Experimental method

X-RAY DIFFRACTION (3.3 Å)