Conservation Analysis of B-Cell Allergen Epitopes to Predict Clinical Cross-Reactivity Between Shellfish and Inhalant Invertebrate Allergens

Nugraha, Roni; Kamath, Sandip D.; Johnston, Elecia B.; Karnaneedi, Shaymaviswanathan; Ruethers, Thimo; Lopata, Andreas L.

doi:10.3389/fimmu.2019.02676

Cited by 53 publications

(50 citation statements)

References 59 publications

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“…Molecular phylogenetic analyses of TM and AK revealed that allergy inducing mite and insect homologues are closer to shrimp TM and AK than molluscs. This observation is supported by a recent study by Nugraha et al where IgE antibody binding epitopes demonstrated shared protein regions of clinical importance [33]. MLC of German cockroach is found to have a closer evolutionary relationship to the black tiger shrimp and whiteleg shrimp, whilst the MLC belonging to American house dust mite is closely related to MLC of a different subset of crustaceans, including, the north-sea shrimp, kuruma shrimp, and red swamp crayfish.…”

Section: Evolutionary Relationship Of Shellfish Allergens Tm Ak Mlcsupporting

confidence: 60%

“…The majority of identified allergens (45%) belong to the group of shellfish and mite allergens. This is not surprising as the shellfish group consists of crustacean (shrimp) and molluscs, which are often combined when analysing related allergens [15,33,34].…”

Section: Discussionmentioning

confidence: 99%

“…However, TM is the major and most recognised shrimp allergen, despite its relatively low abundance. The stronger allergenicity is possible due to being very heat stable and having linear IgE binding epitopes as compared to AK, SCBP, or MLC [8,28,33].…”

Section: Discussionmentioning

confidence: 99%

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Novel allergen discovery through comprehensivede novotranscriptomic analyses of 5 shrimp species

Karnaneedi

Huerlimann

Johnston

et al. 2020

Preprint

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Shellfish allergy affects up to 2% of the world's population and persists for life in most patients. The diagnosis of a shellfish allergy, in particular shrimp, is however often challenging due to the similarity of allergenic proteins in other invertebrates. Despite the clinical importance, the complete allergen repertoire of allergy-causing shrimps remains unclear. Here we mine the complete transcriptome of five frequently consumed shrimp species to identify and compare allergens with all known allergen sources. The transcriptomes were assembled de novo from raw RNA-Seq data of the whiteleg shrimp (Litopenaeus vannamei), black tiger shrimp (Penaeus monodon), banana shrimp (Fenneropenaeus merguiensis), king shrimp (Melicertus latisulcatus), and endeavour shrimp (Metapenaeus endeavouri). Trinity was used to assemble the transcriptome, and Transrate and BUSCO applied to verify the assembly. Blast search with the two major allergen databases, WHO/IUIS Allergen Nomenclature and AllergenOnline, successfully identified all seven known crustacean allergens. Salmon was utilised to measure their relative abundance, demonstrating sarcoplasmic calcium-binding protein, arginine kinase and myosin light chain as highly abundant allergens. In addition, the analyses revealed up to 40 unreported allergens in different shrimp species, including heat shock protein (HSP), alpha-tubulin, chymotrypsin,cyclophilin, beta-enolase, aldolase A, and glyceraldehyde-3-phosphate dehydrogenase (G3PD). Multiple sequence alignment, conducted in Jalview 2.1 with Clustal Omega, demonstrated high homology with allergens from other invertebrates including mites and cockroaches. This first transcriptomic analyses of allergens in a major food source provides a valuable genomic resource for investigating shellfish allergens, comparing invertebrate allergens and developing improved diagnostics and novel immunotherapeutics for food allergy. EJ and AL conceptualized the research objectives. SK, RH, EJ, RN, AT, and AL designed the research methods. RH, NW, and DJ provided the shrimp samples, conducted the RNA extraction and funded the RNA sequencing. SK and RH carried out the de novo transcriptome assembly, transcriptome quality check, BLAST search and relative abundance estimation. SK and RN constructed the allergen reference database and the molecular phylogenetic tree of known shellfish allergens. SK, RN, EJ, TR, AT, SDK, and AL determined the relevant allergens identified within the shrimp transcriptomes and the downstream analyses of these potential allergens. SK, RN, TR, RH, and AL designed the figures and tables. SK and AL wrote the first draft. All authors contributed to manuscript editing and revision.

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Section: Evolutionary Relationship Of Shellfish Allergens Tm Ak Mlcsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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Novel allergen discovery through comprehensivede novotranscriptomic analyses of 5 shrimp species

Karnaneedi

Huerlimann

Johnston

et al. 2020

Preprint

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“…Tropomyosin exhibits a high degree of structural conservation between species 2 . Several studies have shown clinical cross‐reactivity between crustaceans, mollusks, insects, mites, and nematodes is due mainly to shared IgE (B‐cell) epitopes of tropomyosin 3‐5 . However, there is a lack of understanding whether this high degree of structural and sequence conservation among tropomyosins would also lead to cross‐reactive T‐cell epitopes.…”

Section: Introductionmentioning

confidence: 99%

Effect of structural stability on endolysosomal degradation and T‐cell reactivity of major shrimp allergen tropomyosin

Kamath

Scheiblhofer

Johnson

et al. 2020

Allergy

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Background Tropomyosins are highly conserved proteins, an attribute that forms the molecular basis for their IgE antibody cross‐reactivity. Despite sequence similarities, their allergenicity varies greatly between ingested and inhaled invertebrate sources. In this study, we investigated the relationship between the structural stability of different tropomyosins, their endolysosomal degradation patterns, and T‐cell reactivity. Methods We investigated the differences between four tropomyosins—the major shrimp allergen Pen m 1 and the minor allergens Der p 10 (dust mite), Bla g 7 (cockroach), and Ani s 3 (fish parasite)—in terms of IgE binding, structural stability, endolysosomal degradation and subsequent peptide generation, and T‐cell cross‐reactivity in a BALB/c murine model. Results Tropomyosins displayed different melting temperatures, which did not correlate with amino acid sequence similarities. Endolysosomal degradation experiments demonstrated differential proteolytic digestion, as a function of thermal stability, generating different peptide repertoires. Pen m 1 (Tm 42°C) and Der p 10 (Tm 44°C) elicited similar patterns of endolysosomal degradation, but not Bla g 7 (Tm 63°C) or Ani s 3 (Tm 33°C). Pen m 1–specific T‐cell clones, with specificity for regions highly conserved in all four tropomyosins, proliferated weakly to Der p 10, but did not proliferate to Bla g 7 and Ani s 3, indicating lack of T‐cell epitope cross‐reactivity. Conclusions Tropomyosin T‐cell cross‐reactivity, unlike IgE cross‐reactivity, is dependent on structural stability rather than amino acid sequence similarity. These findings contribute to our understanding of cross‐sensitization among different invertebrates and design of suitable T‐cell peptide‐based immunotherapies for shrimp and related allergies.

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“…2 Several studies have shown clinical cross-reactivity between crustaceans, mollusks, insects, mites and nematodes is due mainly to shared IgE (B-cell) epitopes of tropomyosin. [3][4][5] However, there is a lack of understanding whether this high degree of structural and sequence conservation among tropomyosins would also lead to cross-reactive T-cell epitopes. Currently, some T-cell epitopes have only been elucidated for shrimp tropomyosin with little or no data for other allergenic sources, making analysis of T-cell cross-reactivity challenging.…”

Section: Introductionmentioning

confidence: 99%

Effect of structural stability on endolysosomal degradation and T-cell reactivity of major shrimp allergen tropomyosin

Kamath

Scheiblhofer

Johnson

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Tropomyosins are highly conserved proteins, an attribute that forms the molecular basis for their IgE antibody cross-reactivity. Despite structural similarities, their allergenicity varies greatly between ingested and inhaled invertebrate sources. In this study, we investigated the relationship between the structural stability of different tropomyosins, their endolysosomal degradation patterns and T-cell reactivity. Methods:We investigated the differences between four tropomyosins -the major shrimp allergen Pen m 1 and the minor allergens Der p 10 (dust mite), Bla g 7 (cockroach) and Ani s 3 (fish parasite) -in terms of IgE binding, structural stability, endolysosomal degradation and subsequent peptide generation,and T-cell cross-reactivity in a BALB/c murine model. Results:Despite their conserved primary structure and consequent IgE co-reactivity, the invertebrate tropomyosins displayed different protein stabilities. Pen m 1 and Ani s 3, but not Der p 10 and Bla g 7 elicited differential melting temperatures that were pH-dependent. Endolysosomal experiments demonstrated differential degradation, as a function of stability, generating different peptide repertoires.Pen m 1 T-cell clones, with specificity for sequences highly conserved in all four tropomyosins, did not proliferate with Der p 10, Bla g 7 and Ani s 3, indicating that these peptides were not naturally produced for other invertebrate tropomyosins. Conclusions:Our data suggest that, although invertebrate tropomyosins exhibit a high degree of IgE cross-reactivity due to conserved B-cell epitopes, they do not necessarily share identical cross-reactive T-cell epitopes. This is likely due to differential endolysosomal processing as a function of different structural stabilities. Word Count: 3619 14.Kavan D, Man P. MSTools-Web based application for visualization and presentation of HXMS data. Int J Mass Spectrom. 2011;302(1):53-58. 15.Reese G, Viebranz J, Leong-Kee SM, et al. Reduced allergenic potency of VR9-1, a mutant of the major shrimp allergen Pen a 1 (tropomyosin).

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Conservation Analysis of B-Cell Allergen Epitopes to Predict Clinical Cross-Reactivity Between Shellfish and Inhalant Invertebrate Allergens

Cited by 53 publications

References 59 publications

Novel allergen discovery through comprehensivede novotranscriptomic analyses of 5 shrimp species

Novel allergen discovery through comprehensivede novotranscriptomic analyses of 5 shrimp species

Effect of structural stability on endolysosomal degradation and T‐cell reactivity of major shrimp allergen tropomyosin

Effect of structural stability on endolysosomal degradation and T-cell reactivity of major shrimp allergen tropomyosin

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