Haptens protein reactivity

Direct activation of T cells (e.g., derived from patients) Cell damage (reactive oxygen species, apoptosis, necrosis) LLNA (topical application, indication of hapten-protein conjugation) Oral exposure studies (using bystander or reporter antigens to read out immunosensitization)... 

Fig. 9 Possible mechanisms for cell-mediated immune responses triggered by reactive metabolites. The covalent binding of the reactive metabolite modifies hepatic proteins. The death or alteration of one hepatocyte due to mild direct toxicity may lead to the extrusion of a modified protein through the fenestrae of sinusoidal endothelial cells (SEC). The uptake of this haptenized protein by an antigen-presenting cell (APC), such as a Kupffer cell, may lead to the presentation of a metabolite-bound peptide on a major histocompatibility (MHC) class II molecule of the APC, and the recognition of this modified peptide by the T cell receptor (TCR) of a helper T cell. The latter may then provide help to a cytotoxic T lymphocyte recognizing modified peptides presented on the MHC class I molecules of hepatocytes...

Second, the reactive species of a xenobiotic may bind to a protein, altering its antigenicity. The xenobiotic is said to act as a hapten, ie, a small molecule that by itself does not stimulate antibody synthesis but will combine with antibody once formed. The resulting antibodies can then damage the cell by several immunologic mechanisms that grossly perturb normal cellular biochemical processes. 

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