Beryllium-Induced Hypersensitivity: Genetic Susceptibility and Neoantigen Generation

J Immunol. 2016 Jan 1;196(1):22-7. doi: 10.4049/jimmunol.1502011.

Abstract

Chronic beryllium (Be) disease is a granulomatous lung disorder that results from Be exposure in a genetically susceptible host. The disease is characterized by the accumulation of Be-responsive CD4(+) T cells in the lung, and genetic susceptibility is primarily linked to HLA-DPB1 alleles possessing a glutamic acid at position 69 of the β-chain. Recent structural analysis of a Be-specific TCR interacting with a Be-loaded HLA-DP2-peptide complex revealed that Be is coordinated by amino acid residues derived from the HLA-DP2 β-chain and peptide and showed that the TCR does not directly interact with the Be(2+) cation. Rather, the TCR recognizes a modified HLA-DP2-peptide complex with charge and conformational changes. Collectively, these findings provide a structural basis for the development of this occupational lung disease through the ability of Be to induce posttranslational modifications in preexisting HLA-DP2-peptide complexes, resulting in the creation of neoantigens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Berylliosis / genetics*
  • Berylliosis / immunology*
  • Beryllium / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Genetic Predisposition to Disease
  • HLA-DP beta-Chains / genetics
  • HLA-DP beta-Chains / immunology*
  • Humans
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology
  • Lung / immunology
  • Lung / pathology
  • Protein Processing, Post-Translational / genetics
  • Receptors, Antigen, T-Cell / immunology

Substances

  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • HLA-DPw2 antigen
  • Receptors, Antigen, T-Cell
  • Beryllium