Molecular characterization and experimental utility of monoclonal antibodies with specificity for aliphatic di- and polyisocyanates.

Details

• Personal Author:
  Liu J ; Wisnewski AV
• Description:
  Aliphatic di- and polyisocyanates are crucial chemical ingredients in many industrial processes and are a well-recognized cause of occupational asthma. Serologic detection of "chemical epitopes" in biological samples could serve as an exposure surveillance approach toward disease prevention, and thus we sought to generate aliphatic isocyanate-specific monoclonal antibodies (mAbs). Three hybridomas were generated from Balb/c mice immunized with a commercial product containing a combination of uretdione, homopolymer, and monomeric forms of hexamethylene diisocyanate (HDI). Three stable hybridomas were subcloned by limiting dilution, two secreting IgG1? and one secreting IgM? mAb that bind aliphatic di- and polyisocyanates (conjugated to albumin), but not aromatic toluene or methylene diphenyl diisocyanate (TDI or MDI). Each mAb demonstrates slight differences in epitope specificity, for example, recognition of hydrogenated MDI (HMDI) or different carrier proteins (transferrin, actin) reacted with vapor phase HDI, and is encoded by unique recombination of different germline antibody genes, with distinct complementary determining regions. By western blot, all three mAbs detect a molecule with characteristics of an albumin adduct uniquely in urine from mice skin exposed to a mixture of aliphatic di- and polyisocyanate. Together, the data define molecular determinants of humoral immune recognition of aliphatic di- and polyisocyanates through new mAbs, which will serve as useful research reagents and may be applicable to future exposure surveillance efforts. [Description provided by NIOSH]
• Subjects:
  Animals Antibodies Asthma, Occupational Isocyanates Occupational Exposure Occupational Health Safety
• Keywords:
  Author Keywords: Diisocyanate; Aliphatic; Aromatic; Hexamethylene; Uretdione; Homopolymer Diisocyanates; Occupational Asthma; Chemicals; Industrial Exposures; Biological Monitoring; Antibody Response; Animal Studies; Molecular Epidemiology; Hexamethylene Diisocyanate;
• ISSN:
  2167-9436
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Connecticut ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  66-73
• Volume:
  39
• Issue:
  3
• NIOSHTIC Number:
  nn:20065147
• Citation:
  Monoclon Antib Immunodiagn Immunother 2020 Jun; 39(3):66-73
• Contact Point Address:
  Adam V. Wisnewski, Department of Internal Medicine, Yale University School of Medicine, 1 Gilbert Street, TACS-420, New Haven, CT 06519, USA
• Email:
  adam.wisnewski@yale.edu
• CAS Registry Number:
  Diphenylmethane diisocyanate (CAS RN 101-68-8) ; Hexamethylene diisocyanate (CAS RN 822-06-0) ; Toluene diisocyanate (CAS RN 26471-62-5)
• Federal Fiscal Year:
  2020
• Performing Organization:
  Yale University, New Haven, Connecticut
• Peer Reviewed:
  True
• Start Date:
  20160801
• Source Full Name:
  Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
• End Date:
  20200731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:33e74b46703dc31dd8479ca3334d98232c4ad19248db0c06d1a44ba9ef840a6e16c7ee0d498a6ed8b2a7d7b140e5f1dd0660cf194a2890db7ac90b78f0c8c5c8
• Download URL:
  https://stacks.cdc.gov/view/cdc/249351/cdc_249351_DS1.pdf
• File Type:
  [PDF - 369.92 KB ]