[HTML][HTML] Characterization and epitope identification of the T cell response in non-allergic individuals exposed to mouse allergen

A Grifoni, R da Silva Antunes, L Westernberg… - World Allergy …, 2019 - Elsevier
A Grifoni, R da Silva Antunes, L Westernberg, J Pham, G Birrueta, B Peters, A Sette
World Allergy Organization Journal, 2019Elsevier
Background Exposure to airborne allergens is a frequent trigger of respiratory allergy and
asthma in atopic individuals. While allergic patients suffer hypersensitivity reactions to these
allergens, non-allergic individuals do not exhibit clinical symptoms despite environmental
exposure to these ubiquitous allergen sources. The aim of this study was to characterize T
cell responses in non-allergic laboratory workers, who are heavily exposed to mice
allergens (Exposed Non-Allergics, ENA) and compare this data to previously published T …
Background
Exposure to airborne allergens is a frequent trigger of respiratory allergy and asthma in atopic individuals. While allergic patients suffer hypersensitivity reactions to these allergens, non-allergic individuals do not exhibit clinical symptoms despite environmental exposure to these ubiquitous allergen sources. The aim of this study was to characterize T cell responses in non-allergic laboratory workers, who are heavily exposed to mice allergens (Exposed Non-Allergics, ENA) and compare this data to previously published T cell responses measured in mouse (MO)-allergic patients. METHODS: Peripheral mononuclear cells (PBMC) from ENA subjects were expanded for 2 weeks in vitro with mouse urine extract and screened for IFNγ and IL-5 cytokine production in response to mouse antigen-derived peptides by ELISPOT. Ex vivo T cell reactivity in the ENA cohort was performed after 6hr stimulation with peptide pools by intracellular staining of CD154.
Results
Vigorous responses were detected, associated with 147 epitopes derived from 16 mouse antigens. As expected, responses in ENA subjects were somewhat lower than those observed in MO-allergics for both responder frequency and overall response magnitude. While responses in allergics were polarized towards IL-5 production and associated with low IFNγ production, ENA responses were not polarized. The composition of targeted antigens and epitopes was overall similar between the two cohorts, with the majority of T cell reactivity directed against Mus m 1 and other major urinary proteins. However, kappa-casein precursor and odorant binding protein Ib were more abundantly recognized in MO-allergics compared to ENA subjects. Additionally, T cell responses against oligopeptides derived from the low molecular weight fraction of mouse urine were also assessed. Interestingly, no difference in the response frequency, magnitude or polarization between MO-allergic and ENA individuals was observed. Finally, assessment of ex vivo T cell activation also revealed T cell reactivity in the ENA cohort, with a non-significant trend for lower responses compared to MO-allergics.
Conclusion
Exposure to mouse induces potent T cell responses in non-allergic individuals, targeting similar epitopes as seen in allergic patients.
Elsevier