Exploiting Inhibitory Siglecs to Combat Food Allergies
Technical Report,30 Sep 2018,29 Sep 2019
The Scripps Research Institute La Jolla United States
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During the third year of this award, we have continued to generate important data related to targeting of CD22 on B cells and CD33 on mast cells to abrogate food allergies. With our prophylactic and therapeutic models utilizing CD22 STALs established in the first two years of the award, we have now moved onto mechanistic studies. In particular, we have used peanut allergen tetramers to enrich peanut-specific B cells from mice. Optimization of the tetramer reagents using Ara h 1, 2, 3, and 6 proteins was completed, and initial studies carried out with mouse splenocytes. Using human CD22 transgenic mice, we have been able to demonstrate in our conferred sensitization allergy protocol that full tolerance can be generated to Ah1 through human CD22. In terms of targeting CD33 in this past year, we have moved into human whole blood basophil activation assays BATs to demonstrate the peanut proteins coupled with CD33 ligand can suppress degranulation responses ex vivo. Our initial studies indicate that simultaneous engagement of human CD33 and Ara h 2-IgE leads to suppression of further Ara h 2-induced degranulation. The results offer promise for developing therapies for patients with allergies and allergic asthma to desensitize mast cells and improve approaches for inducing tolerance to the offending antigens.
- Medicine and Medical Research