Predicting cross reactivity between the fire ant venom allergen Sol i 3 and the antigen 5 from vespid venoms based on...

The fire ant Solenopsis invicta is an aggressive invasive species whose venom frequently triggers hypersensitivity reactions, including severe anaphylaxis. In endemic regions, its stings represent a significant cause of Hymenoptera-related allergy. Four venom allergens have been identified - phospholipase A1 (Sol i 1), antigen 2 (Sol i 2), antigen 3 (Sol i 3), and antigen 4 (Sol i 4) - with Sol i 3 recognized as the predominant sensitizer. However, the molecular determinants that drive Sol i 3 allergenicity and its potential cross-reactivity with other Hymenoptera venoms remain insufficiently understood. This study identified the linear immunoglobulin E (IgE) epitopes of Sol i 3 and examined their recognition by sera from yellow jacket venom (YJV) - and Polistes wasp-allergic patients. Two linear epitopes were mapped: Sol i 3_e1 (ELRQRVASGKEMRG) and Sol i 3_e2 (WAKTTKIGCGRIMF). Although Sol i 3 exhibits limited sequence and structural similarity to other antigen 5 proteins, it contains a conserved immunoreactive core (WAKTTK), analogous to the WAKTKE motif described for the allergen Poly p 5 from Polybia paulista. This conserved region may represent a shared epitope contributing to cross-reactivity among Hymenoptera venoms. Consistently, sera from P. dominula-sensitized patients and YJV-sensitized patients recognized Sol i 3_e2. These findings define key B-cell epitopes of Sol i 3 and reveal a conserved motif that may underlie cross-reactivity, offering implications for improved diagnosis and immunotherapy.