FOOD ALLERGIES ARE A GROWING FOOD SAFETY AND PUBLIC HEALTH CONCERN THAT AFFECT AN ESTIMATED 15 MILLION AMERICANS INCLUDING 4-6% OF CHILDREN AND 4% OF ADULTS. MAMMALIAN MEAT ALLERGY IS AN EMERGENT ALLERGY THAT IS BECOMING INCREASINGLY WIDESPREAD IN AREAS WHERE TICKS ARE ENDEMIC IN THE UNITED STATES. A RAPIDLY INCREASING BODY OF RESEARCH PROPOSES THAT BITES FROM THE LONE-STAR TICK (AMBLYOMMA AMERICANUM) ARE CAUSING THIS UNUSUAL DELAYED-TYPE ALLERGIC REACTION TO RED MEAT. SENSITIZATION TO OLIGOSACCHARIDE GALACTOSE-Α-1,3-GALACTOSE (Α-GAL) HAS BEEN SHOWN TO BE THE MECHANISM OF ANAPHYLACTIC REACTION IN RED MEAT ALLERGY FOLLOWING TICK BITES. OUR OBJECTIVE IN THIS GRANT APPLICATION IS TO UTILIZE AN IN VITRO MAST CELL BASED HISTAMINE RELEASE ASSAY TO IDENTIFY AND CHARACTERIZE Α-GAL CONTAINING PROTEINS IN THE LONE-STAR TICK SALIVA. IN THIS GRANT APPLICATION, WE WILL TEST OUR HYPOTHESIS THAT RED MEAT ALLERGY ALLERGY INDUCING TICK SALIVA FACTORS CAN BE IDENTIFIED, ISOLATED, AND CONFIRMED BY CELL-BASED SECRETION ASSAYS. WE WILL TEST OUR HYPOTHESIS BY USING A COMBINATION OF IMMUNOLOGICAL, MOLECULAR, BIOCHEMICAL, REVERSE GENETIC, AND SYSTEM APPROACHES TO PURSUE THESE AIMS: 1) IDENTIFY TICK SALIVA FACTORS RESPONSIBLE FOR THE PRODUCTION OF IGE ANTIBODIES USING AN IN VITRO MAST CELL DEGRANULATION ASSAY, AND 2) VALIDATE THE FUNCTIONAL ROLE OF THE IDENTIFIED TICK ANTIGENS TO STIMULATE HISTAMINE RELEASE. THIS STUDY WILL ESTABLISH THE CAUSE OF SEVERE ANAPHYLAXIS AND IDENTIFY THE TICK MOLECULES RESPONSIBLE FOR RED MEAT ALLERGY. IT WILL PAVE THE WAY TO SAFEGUARD AT-RISK POPULATIONS.

The University Of Southern Mississippi

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