ALLERGY TO ANTIBIOTICS - T-CELL RECOGNITION OF AMOXICILLIN IS HLA-DR RESTRICTED AND DOES NOT REQUIRE ANTIGEN-PROCESSING

Allergic immune responses are initiated and maintained by T cells that recognize peptidic fragments of allergens in the context of major his tocompatibility complex (MHC) class II molecules, An anomaly of this m odel exists in the T-cell response to haptens. Haptens are nonpeptide antigens that alone are too small to provoke an immune response. Never theless, T-cell responses to haptenic allergens clearly occur and are critically involved in allergic immune responses to drugs such as peni cillin. Although the mechanisms that generate T-cell epitopes from pro tein antigens are well understood, haptens create T-cell epitopes by a lternative mechanisms. These may include binding of haptens directly t o preformed MHC-peptide complexes on the cell surface, or indirect ass ociation with MHC molecules after conjugation with self cell surface o r serum proteins that are then processed and presented as haptenated p eptide antigens. Which of these unorthodox mechanisms of epitope gener ation is dominant in allergy to penicillin is unknown. This study aims to determine the nature of the epitopes recognized by amoxicillin-spe cific T cells from allergic donors, and to clarify whether T-cell resp onses to penicillin antibiotics are MHC-restricted and require haptena ted self proteins to be processed before recognition. Human T-cell lin es specific for amoxicillin were raised and used in assays with proces sing-disabled and MHC-class II-typed antigen-presenting cells to deter mine the MHC restriction and processing requirements of T cells recogn izing amoxicillin. Fixation of antigen presenting cells with paraforma ldehyde, before or after pulsing with amoxicillin, established that T cells can recognize amoxicillin-containing epitopes with a similar eff iciency irrespective of whether the antigenic conjugate has been inter nalized and processed, These results suggest that amoxicillin can bind directly to preformed MHC-peptide complexes and need not necessarily involve the processing of haptenated self carrier proteins before reco gnition of the conjugate by amoxicillin-specific T cells.