Effect of structural stability on endolysosomal degradation and T-cell reactivity of major shrimp allergen tropomyosin
Kamath, Sandip D., Scheiblhofer, Sandra, Johnson, Christopher M., Machado, Yoan, McLean, Thomas, Taki, Aya C., Ramsland, Paul A., Iyer, Swati, Joubert, Isabella, Hofer, Heidi, Wallner, Michael, Thalhamer, Josef, Rolland, Jennifer, O’Hehir, Robyn, Briza, Peter, Ferreira, Fatima, Weiss, Richard, and Lopata, Andreas L. (2020) Effect of structural stability on endolysosomal degradation and T-cell reactivity of major shrimp allergen tropomyosin. Allergy, 75 (11). pp. 2909-2919.
|
PDF (Published version)
- Published Version
Available under License Creative Commons Attribution. Download (1MB) | Preview |
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 ID: | 63528 |
|---|---|
| Item Type: | Article (Research - C1) |
| ISSN: | 1398-9995 |
| Keywords: | cross-reactivity, endolysosomal degradation, shrimp allergy, T cell, tropomyosin |
| Copyright Information: | © 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Date Deposited: | 22 Jul 2020 04:02 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320401 Allergy @ 70% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320506 Medical biochemistry - proteins and peptides (incl. medical proteomics) @ 15% 31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310112 Structural biology (incl. macromolecular modelling) @ 15% |
| SEO Codes: | 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 40% 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 60% |
| Downloads: |
Total: 7 Last 12 Months: 6 |
| More Statistics |
Actions (Repository Staff Only)
 |
Item Control Page |