PENICILLOYL PEPTIDES ARE RECOGNIZED AS T-CELL ANTIGENIC DETERMINANTS IN PENICILLIN ALLERGY

Although hapten immune responses have been intensively:studied in the mouse, very little is known about hapten determinants involved in huma n allergic reactions. Penicillins, as chemically reactive compounds of low molecular weight, constitute typical examples of hapten allergens for humans. Penicillins become immunogenic only after covalent bindin g to carrier proteins and in this form frequently induce IgE-mediated allergic reactions in patients subjected to antibiotic treatment. Howe ver, our previous data strongly indicated that penicillins also form p art of the epitopes contacting the antigen receptors of beta lactam-sp ecific T cells in allergic individuals. We have therefore investigated the molecular constraints involved in the T cell immune response to p enicillin G (Pen G). Designer peptides containing a DRB10401-binding motif and covalently modified with Pen G via a lysine E-amino group we re found to induce proliferation of Pen G-specific T cell clones. A pr ecise positioning of the hapten molecule on the peptide backbone was r equired for optimal T cell recognition. Furthermore, we extended these observations from our designer peptides to show that a peptide sequen ce derived from a natural DRB11101-binding peptide modified in vitro with Pen G, also acquired antigenic properties. Our data for the first time provide insight into the manner in which allergenic haptens are recognized by human T cells involved in allergic reactions to drugs an d suggest possible mechanisms leading to the onset of these adverse im mune responses.