Abstract
BackgroundTropomyosins 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.MethodsWe 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.ResultsTropomyosins 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.ConclusionsTropomyosin 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.
Highlights
The tropomyosin protein family is one of the largest allergen families containing over 60 identified and characterized allergens.[1]
Tropomyosin is the primary sensitizer in various crustacean and mollusk species, and a key player in our understanding of clinical cross-reactivity in shrimp-allergic patients on exposure to other invertebrate sources such as insects,[16,17] mites,[18] nematodes,[19] and more recently, even vertebrates such as fish.[20,21]
We sought to understand the fundamental relationship between allergenic invertebrate tropomyosins in terms of their structural stabilities, endolysosomal degradation patterns, and T-cell reactivity
Summary
The tropomyosin protein family is one of the largest allergen families containing over 60 identified and characterized allergens.[1]. Crustacean and mollusk shellfish tropomyosins are major allergens, shrimp tropomyosin (Pen m 1), with more than 80% of shrimp-allergic patients being sensitized to this allergen These major food allergens have been shown to be extremely thermostable and to withstand food-processing activities.[9,10] Some other invertebrate tropomyosins from sources such as mites and insects are considered only as minor allergens. In a murine model using Pen m 1 peptide-specific T-cell clones with conserved sequence identity, we found only limited T-cell cross-reactivity with Der p 10, and none with Bla g 7 and Ani s 3. Conserved invertebrate tropomyosins may share IgE epitopes leading to clinical cross-reactivity; presence of shared identical T-cell epitopes seems to be dependent on similarities in structural stability as opposed to amino acid sequence identity. Our findings have implications for understanding possible modes of sensitization as well as the design of suitable tropomyosin preparations for specific immunotherapy for shrimp and related allergies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
