Because most drugs are low molecular weight chemicals, in theory too small to be able to stimulate the immune system, it has long been assumed that the drug or a reactive metabolite must first bind covalently to a macromolecule such as a protein, forming a multivalent conjugate that is processed and presented by the immune system to T cells. Probably, the clearest example of drug haptenation is that which occurs with penicilline, which is chemically reactive and undergoes stable covalent binding to proteins or peptides, resulting in the creation of an immunogenic self protein.
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