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

Mol Immunol. 2018 Jul;99:1-8. doi: 10.1016/j.molimm.2018.03.022. Epub 2018 Apr 6.

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.

Keywords: Allergens; Birch pollen allergen; Pectate lyase; Physical-chemical property motifs; Profilin; human microbiome.

Publication types

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

MeSH terms

  • Allergens / chemistry*
  • Allergens / immunology*
  • Cross Reactions / immunology
  • Epitopes / chemistry
  • Epitopes / immunology
  • Fruit / chemistry
  • Fruit / immunology
  • Humans
  • Immunoglobulin E / chemistry
  • Immunoglobulin E / immunology
  • Nuts / chemistry
  • Nuts / immunology
  • Plant Proteins / chemistry
  • Plant Proteins / immunology
  • Pollen / chemistry
  • Pollen / immunology
  • Polysaccharide-Lyases / chemistry
  • Polysaccharide-Lyases / immunology
  • Profilins / chemistry
  • Profilins / immunology

Substances

  • Allergens
  • Epitopes
  • Plant Proteins
  • Profilins
  • Immunoglobulin E
  • Polysaccharide-Lyases
  • pectate lyase