Re: What is the real mechanism for penicillin allergy?

It is true that the membrane of the T helper cell should not be antigenic by itself. However, the penicillin binds to many sites on the membrane. The arrangment of these determinants on the membrane is what the immune system reacts to. At this point, the small penicillin molecule appears to the immune system to be a large, multi-determinant antigen, which, of course, is fully capable of elliciting an immune response. Below is an excerpt from a recent review of drug allergies:

Drug metabolism typically occurs as 2 different steps, phase I and phase II reactions. Phase I reactions are oxidation-reduction or hydrolysis reactions, and phase II reactions are conjugation reactions that result in the formation of inactive compounds that are easily excreted. Most often, a reactive metabolite formed by phase I metabolism is promptly detoxified and eliminated. However, reactive drug metabolites that are not detoxified may bind to proteins or nucleic acids, causing cellular necrosis or the production of an altered gene product, respectively, as part of a directly toxic effect. Reactive metabolites of sulfonamides have been shown to act in this manner. 11,12 Alternatively, reactive metabolites may act as haptens that bind covalently with cellular macromolecules such as serum proteins 6,7 or cell-surface membranes. 13 Such binding results in the formation of large, multivalent immunogens that may initiate an immune response. It is thought that hypersensitivity reactions to antibiotics may occur by way of this mechanism.

1. BALDO, B. A.. Penicillins and cephalosporins as allergens - structural aspects of recognition and cross-reactions. Clinical & Experimental Allergy 29(6):744-749, June 1999.
2. PADOVAN, E.. T-cell response in penicillin allergy. Clinical & Experimental Allergy, Supplement. 28 Supplement 4:33-36, September 1998.
3. Weltzien, Hans Ulrich. Padovan, Elisabetta. Molecular Features of Penicillin Allergy. Journal of Investigative Dermatology 110(3):203-206, March 1998.
4. Horton, H. 1. Weston, S. D. 2. Hewitt, C. R. A. 2. Allergy to antibiotics: T-cell recognition of amoxicillin is HLA-DR restricted and does not require antigen processing. Allergy 53(1):83-88, January 1998.