The Journal of Allergy and Clinical Immunology
Volume 121, Issue 2 , Pages 320-325 , February 2008

“Accentuate the negative, eliminate the positive”: Engineering allergy therapeutics to block allergic reactivity through negative signaling

  • Andrew Saxon, MD

      Affiliations

    • Department of Medicine, University of California, Los Angeles, Calif
    • Corresponding Author InformationReprint requests: Andrew Saxon, MD, 52-262 CHS, Department of Medicine, 10833 Le Conte Ave, University of California, Los Angeles CA, 90095-16908.
    • ,
  • Chris Kepley, PhD

      Affiliations

    • Department of Internal Medicine, Virginia Commonwealth University Health Systems, Richmond, Va
    • ,
  • Ke Zhang, MD, PhD

      Affiliations

    • Department of Medicine, University of California, Los Angeles, Calif

Received 31 August 2007 ,Revised 15 October 2007 ,Accepted 16 October 2007.

  • Image Result

    Action mode of the genetically engineered GE2 and GFD. Antigen cross-linking of 2 FcεRIs and induction of activation with enhancement of Syk and other downstream signaling molecules are diagrammed in

    Action mode of the genetically engineered GE2 and GFD. Antigen cross-linking of 2 FcεRIs and induction of activation with enhancement of Syk and other downstream signaling molecules are diagrammed in the middle panel, where FcγRII is unoccupied. GE2 co–cross-linking FcγRIIb to FcεRI, which results in the inhibition of signaling events downstream of the FcεRI immunoreceptor tyrosine–based activation motif (ITAM), is shown in the left panel, and the cross-linking mediated by GFD is presented in the right panel. A similar mode of action has been shown for mouse GE2.16 ITIM, Immunoreceptor tyrosine–based inhibitory motif.

 Supported by United States Public Health Service–National Institutes of Health grant AI-15251 and a gift from the Food Allergy Initiative. C.L.K. and K.Z. were supported by the Food Allergy and Anaphylaxis Network.

 Disclosure of potential conflict of interest: A. Saxon and K. Zhang have patent licensing arrangements with the University of California. C. Kepley has received grant support from the Food Allergy Anaphylaxis Network.

PII: S0091-6749(07)01959-8

doi: 10.1016/j.jaci.2007.10.017

The Journal of Allergy and Clinical Immunology
Volume 121, Issue 2 , Pages 320-325 , February 2008

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