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Predictive in silico binding algorithms reveal HLA specificities and autoallergen peptides associated with atopic dermatitis - PubMed

Predictive in silico binding algorithms reveal HLA specificities and autoallergen peptides associated with atopic dermatitis

Jan J Gong et al. Arch Dermatol Res. 2020 Nov.

Abstract

Atopic dermatitis (AD) is a skin disease that results from a combination of skin barrier dysfunction and immune dysregulation. The immune dysregulation is often associated with IgE sensitivity. There is also evidence that autoallergens Hom s 1, 2, 3, and 4 play a role in AD; it is possible that patients with specific HLA subtypes are predisposed to autoreactivity due to increased presentation of autoallergen peptides. The goal of our study was to use in silico epitope prediction platforms as an approach to identify HLA subtypes that may preferentially bind autoallergen peptides and are thus candidates for further study. Considering the previously described association of DRB1 alleles with AD and progression of disease, emphasis was placed on DRB1. Certain DRB1 alleles (08:04, 11:01, and 11:04) were identified by both algorithms to bind a significant percent of the generated autoallergen peptides. Conversely, autoallergen core peptide sequences FRQLSHRFH and IRAKLRLQA (Hom s 1), IRKSKNILF (Hom s 2), FKWVPVTDS and MAAIEKVRK (Hom s 3), and FRYFATLKV (Hom s 4) were predicted to bind many DRB1 alleles and, thus, may play a role in the pathogenesis of AD. Our findings provide candidate DRB1 alleles and autoallergen epitopes that will guide future studies exploring the relationship between DRB1 subtype and autoreactivity in AD. A similar approach can be used for any antigen that has been associated with an IgE response and AD.

Keywords: Atopic dermatitis; Autoreactivity; HLA alleles.

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Conflict of interest statement

Competing Interests

The authors have declared no conflicts of interest.

Figures

Figure 1.
Figure 1.. HLA-DRB1 alleles that have the greatest percent of predicted binders among all autoallergens.

(A) Number of predicted binders for each alleles, expressed as a percent of all epitopes. (*) denotes that the allele was in the top five alleles ranked by percent of predicted binders for the given autoallergen; faded cells indicate that the allele was not in the top five alleles with the most predicted binders for the given autoallergen. Alleles that appeared in the top five for more than one autoallergen are listed, and alleles that overlap between the IEDB and NetMHCIIpan algorithms are bold and italicized. (B) Amino acid sequences at key positions implicated in binding pockets in the antigen presenting domain of the MHC molecule. Residues are categorized as hydrophobic, polar uncharged, negatively charged, and positively charged.

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