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Title: Accelerator mass spectrometry detection of beryllium ions in the antigen processing and presentation pathway

We report that exposure to small amounts of beryllium (Be) can result in beryllium sensitization and progression to Chronic Beryllium Disease (CBD). In CBD, beryllium is presented to Be-responsive T-cells by professional antigen-presenting cells (APC). This presentation drives T-cell proliferation and pro-inflammatory cytokine (IL-2, TNFα, and IFNγ) production and leads to granuloma formation. The mechanism by which beryllium enters an APC and is processed to become part of the beryllium antigen complex has not yet been elucidated. Developing techniques for beryllium detection with enough sensitivity has presented a barrier to further investigation. The objective of this study was to demonstrate that Accelerator Mass Spectrometry (AMS) is sensitive enough to quantify the amount of beryllium presented by APC to stimulate Be-responsive T-cells. To achieve this goal, APC - which may or may not stimulate Be-responsive T-cells - were cultured with Be-ferritin. Then, by utilizing AMS, the amount of beryllium processed for presentation was determined. Further, IFNγ intracellular cytokine assays were performed to demonstrate that Be-ferritin (at levels used in the experiments) could stimulate Be-responsive T-cells when presented by an APC of the correct HLA type (HLA-DP0201). The results indicated that Be-responsive T-cells expressed IFNγ only when APC with the correct HLAmore » type were able to process Be for presentation. Utilizing AMS, we determined that APC with HLA-DP0201 had membrane fractions containing 0.17-0.59 ng Be and APC with HLA-DP0401 had membrane fractions bearing 0.40-0.45 ng Be. However, HLA-DP0401 APC had 20-times more Be associated with the whole cells (57.68-61.12 ng) then HLA-DP0201 APC (0.90-3.49 ng). As these findings demonstrate, AMS detection of picogram levels of Be processed by APC is possible. Further, regardless of form, Be requires processing by APC to successfully stimulate Be-responsive T-cells to generate IFNγ.« less
 [1] ;  [2] ;  [3] ;  [4] ;  [2]
  1. Univ. of Colorado Denver, Aurora CO (United States). Anschutz Medical Campus
  2. Univ. of Colorado Denver, Aurora CO (United States). Anschutz Medical Campus
  3. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Chemical Sciences Division
  4. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences Biotechnology Division
Publication Date:
OSTI Identifier:
Accepted Manuscript
Journal Name:
Journal of Immunotoxicology
Additional Journal Information:
Journal Volume: 12; Journal Issue: 2; Journal ID: ISSN 1547-691X
Taylor & Francis
Research Org:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Org:
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES Beryllium; accelerator mass spectrometry (AMS); chronic beryllium disease; metal antigen; metal processing