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

Kamath, S.D., Scheiblhofer, S., Johnson, C.M., Machado, Y., McLean, T., Taki, A.C., Ramsland, P.A., Iyer, S., Joubert, I., Hofer, H., Wallner, M., Thalhamer, J., Rolland, J., O’Hehir, R., Briza, P., Ferreira, F., Weiss, R. and Lopata, A.L. (2020) Effect of structural stability on endolysosomal degradation and T‐cell reactivity of major shrimp allergen tropomyosin. Allergy, 75 (11). pp. 2909-2919.

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Abstract

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.

Item Type: Journal Article
Publisher: Wiley-Blackwell
Copyright: © 2020 The Authors.
URI: http://researchrepository.murdoch.edu.au/id/eprint/63733
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