Food allergies are an increasing health problem throughout the developed world. Among these, peanut allergy is particularly significant, due to its exceptional severity and frequent lifelong duration. Much of its aetiology remains unclear. In particular, it remains unknown why, unlike other food allergies, peanut allergy incidence correlates poorly with average dietary peanut consumption. A popular explanation for this discrepancy is that peanut allergy is more common in regions where predominantly dry-roasted (DR) peanuts are consumed, leading to speculation that DR-induced chemical modifications may contribute to pathological T<sub>h</sub>2 responses in humans. Yet to date, no research group has demonstrated an enhanced immunogenicity of DR peanuts relative to raw in a murine model of sensitisation. This thesis begins with the hypothesis that dry-roasting does indeed alter the chemical composition of peanut proteins in such a way as to increase immunogenicity and allergenicity. To test this hypothesis robustly, I have first addressed flaws in previous studies by developing a methodology to thoroughly characterise samples of raw and DR peanut protein, as well as purifying samples of individual peanut allergens. Using these samples, I have demonstrated an enhanced immunogenicity of DR peanut protein relative to raw, in intragastric, subcutaneous and epicutaneous models of mouse sensitisation, and furthermore, that such enhanced responses feature a pronounced T<sub>h</sub>2 bias and functional IgE production. I will present evidence that this difference is not caused by either protein aggregation or the presence of other non-protein substances, but is due to an intrinsic property of the DR peanut proteins. I will go on to clarify candidate molecular mechanisms of this effect, examining several putative receptors and probing the effects of roasting on dendritic cell binding and interactions of peanut proteins. I conclude in light of these investigations that the dry-roasting hypothesis remains the most plausible explanation for the epidemiological distribution of peanut allergy, although many additional questions remain regarding the nature of the chemical modifications produced by roasting and the molecular basis of their recognition by the immune system.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:604396 |
| Date | January 2013 |
| Creators | Hillson, William Rawstron |
| Contributors | Sattentau, Quentin J.; Moghaddam, Amin E. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:88d64b79-a7e6-4e41-acee-47c215d39f6b |
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