Tolerance to Self and Allergenicity Figure 5. High levels of amino acid identity with human proteins are associated with decreased allergenicity. A, The prevalence of IgE to a natural purified or recombinant allergen (each dot represents a single allergen) and B, the absolute number of allergens (major, minor or unknown prevalence) as a function of the % amino acid identity with homologous human proteins (x-axis). Dotted line (A) separates major and minor allergens. doi:10.1371/journal.pone.0040552.g005 Homo sapiens protein database were downloaded from genome website (ftp://ftp.ncbi.nlm.nih.gov/genomes/). NCBI Bioinformatics Tools and Analysis The BlastP program [42] was used to compare the amino acid sequence of the list of allergens with each genome-predicted protein of the microbial/helminthic organisms and humans as previously described [43] Spreadsheets were generated containing the accession number of the protein-coding gene, E-value and percentage of identity at the amino acid level for the best homologue for each allergen along with IgE prevalences and hyperlinked literature references and can be found in Tables S1 and S2. Further analysis, statistics and graphs were performed using Excel (Microsoft Corporation) and Graphpad Prism v5.0 (GraphPad Software Inc., San Diego, California). Supporting Information Figure S1 Negative correlation between High levels of amino acid identity with human proteins was also observed for a group of non-redundant allergens. The prevalence of IgE to a natural purified or recombinant allergen is References 1. Aas K (1978) What makes an allergen an allergen. Allergy 33: 3–14. 2. Poulsen LK (2009) What makes an allergen more than an allergen? Clin Exp Allergy 39: 623–625. 3. Radauer C, Bublin M, Wagner S, Mari A, Breiteneder H (2008) Allergens are distributed into few protein families and possess a restricted number of biochemical functions. J Allergy Clin Immunol 121: 847–852 e847. 4. Shea KM, Truckner RT, Weber RW, Peden DB (2008) Climate change and allergic disease. J Allergy Clin Immunol 122: 443–453; quiz 454–445. 5. Vercelli D (2010) Gene-environment interactions in asthma and allergy: the end of the beginning? Curr Opin Allergy Clin Immunol. 6. Traidl-Hoffmann C, Jakob T, Behrendt H (2009) Determinants of allergenicity. The Journal of allergy and clinical immunology 123: 558–566. 7. Sokol CL, Barton GM, Farr AG, Medzhitov R (2008) A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat Immunol 9: 310– 318. 8. Steinfelder S, Andersen JF, Cannons JL, Feng CG, Joshi M, et al. (2009) The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1). J Exp Med 206: 1681– 1690. Table S3 (DOCX) represented in the y-axis and the level of identity with human proteins in the x-axis. Each dot represents a single allergen of the list showed in Table S3. (TIF) Table S1 List of all allergens and the respective homologous proteins in the microbes and human genomes. (XLSX) Table S2 List of allergens families (ALLFam) analyzed and a representative allergen of each family. (DOCX) Allergens used in Figure S1. Author Contributions Conceived and designed the experiments: HCS SB JMCR TN. Performed the experiments: HCS SB. Analyzed the data: HCS SB JMCR TN. Contributed reagents/materials/analysis tools: HCS JMCR TN. Wrote the paper: HCS TN. 9. Everts B, Perona-Wright G, Smits HH, Hokke CH, van der Ham AJ, et al. (2009) Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses. J Exp Med 206: 1673–1680. 10. Okano M, Satoskar AR, Nishizaki K, Harn DA Jr. (2001) Lacto-N-fucopentaose III found on Schistosoma mansoni egg antigens functions as adjuvant for proteins by inducing Th2-type response. J Immunol 167: 442–450. 11. Okano M, Satoskar AR, Nishizaki K, Abe M, Harn DA Jr. (1999) Induction of Th2 responses and IgE is largely due to carbohydrates functioning as adjuvants on Schistosoma mansoni egg antigens. J Immunol 163: 6712–6717. 12. Strachan DP (1989) Hay fever, hygiene, and household size. BMJ 299: 1259– 1260. 13. Matricardi PM, Rosmini F, Panetta V, Ferrigno L, Bonini S (2002) Hay fever and asthma in relation to markers of infection in the United States. J Allergy Clin Immunol 110: 381–387. 14. Schaub B, Lauener R, von Mutius E (2006) The many faces of the hygiene hypothesis. J Allergy Clin Immunol 117: 969–977; quiz 978. 15. Fernandes JF, Taketomi EA, Mineo JR, Miranda DO, Alves R, et al. (2010) Antibody and cytokine responses to house dust mite allergens and Toxoplasma gondii antigens in atopic and non-atopic Brazilian subjects. Clin Immunol 136: 148–156. PLoS ONE | www.plosone.org 7 July 2012 | Volume 7 | Issue 7 | e40552