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

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

Author information

1
Sealy Center for Structural Biology and Molecular Biophysics, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0304, United States.
2
Southern Regional Research Center, U.S. Department of Agriculture, Agriculture Research Service, 1100 Robert E. Lee Boulevard, New Orleans, LA 70124, United States.
3
Sealy Center for Structural Biology and Molecular Biophysics, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0304, United States. Electronic address: webraun@utmb.edu.

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

PMID:
29627609
PMCID:
PMC5994374
[Available on 2019-07-01]
DOI:
10.1016/j.molimm.2018.03.022
[Indexed for MEDLINE]

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