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

Beryllium-Induced Hypersensitivity: Genetic Susceptibility and Neoantigen Generation.

Author information

1
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; andrew.fontenot@ucdenver.edu.
2
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045;
3
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206; and Department of Biomedical Research, National Jewish Health, Denver, CO 80206.
4
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; Department of Biomedical Research, National Jewish Health, Denver, CO 80206.

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.

PMID:
26685315
PMCID:
PMC4685955
DOI:
10.4049/jimmunol.1502011
[Indexed for MEDLINE]
Free PMC Article

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