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Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy. In this study, we investigated the presence of α-gal in four tick species: the lone-star tick ( Amblyomma americanum ), the Gulf-Coast tick ( Amblyomma maculatum ), the American dog tick ( Dermacentor variabilis ), and the black-legged tick ( Ixodes scapularis ) by using a combination of immunoproteomic approach and, carbohydrate analysis. Anti-α-gal antibodies identified α-gal in the salivary glands of both  Am. americanum  and  Ix. scapularis , while  Am. maculatum  and  De. variabilis  appeared to lack the carbohydrate. PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands. Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.  Am. americanum  ticks were fed on human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal. N-linked glycan analysis revealed that  Am. americanum  and  Ix. scapularis  have α-gal in their saliva and salivary glands, but  Am. maculatum  contains no detectable quantity. Consistent with the glycan analysis, salivary samples from  Am. americanum  and  Ix. scapularis  stimulated activation of basophils primed with plasma from α-gal allergic subjects. Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans. Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.

Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy