Distinguishing allergens from non-allergenic homologues using Physical–Chemical Property (PCP) motifs

Wenzhe Lu, Surendra S. Negi, Catherine H. Schein, Soheila J. Maleki, Barry K. Hurlburt, Werner Braun

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Quantitative guidelines to distinguish allergenic proteins from related, but non-allergenic ones are urgently needed for regulatory agencies, biotech companies and physicians. In a previous study, we found that allergenic proteins populate a relatively small number of protein families, as characterized by the Pfam database. However, these families also contain non-allergenic proteins, meaning that allergenic determinants must lie within more discrete regions of the sequence. Thus, new methods are needed to discriminate allergenic proteins within those families. Physical–Chemical Properties (PCP)-motifs specific for allergens within a Pfam class were determined for 17 highly populated protein domains. A novel scoring method based on PCP-motifs that characterize known allergenic proteins within these families was developed, and validated for those domains. The motif scores distinguished sequences of allergens from a large selection of 80,000 randomly selected non-allergenic sequences. The motif scores for the birch pollen allergen (Bet v 1) family, which also contains related fruit and nut allergens, correlated better than global sequence similarities with clinically observed cross-reactivities among those allergens. Further, we demonstrated that the average scores of allergen specific motifs for allergenic profilins are significantly different from the scores of non-allergenic profilins. Several of the selective motifs coincide with experimentally determined IgE epitopes of allergenic profilins. The motifs also discriminated allergenic pectate lyases, including Jun a 1 from mountain cedar pollen, from similar proteins in the human microbiome, which can be assumed to be non-allergens. The latter lacked key motifs characteristic of the known allergens, some of which correlate with known IgE binding sites.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalMolecular Immunology
Volume99
DOIs
StatePublished - Jul 2018

Keywords

  • Allergens
  • Birch pollen allergen
  • Pectate lyase
  • Physical-chemical property motifs
  • Profilin
  • human microbiome

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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